<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  9.6.8042.36810 -->
<!--Based on XBRL 2.1-->
<!--Created on: 3/31/2022 11:04:08 AM-->
<!--Modified on: 3/31/2022 11:04:08 AM-->
<link:linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#StatementConsolidatedStatementsOfOperations" roleURI="http://www.protalix.com/role/StatementConsolidatedStatementsOfOperations" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#StatementConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" roleURI="http://www.protalix.com/role/StatementConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureConvertibleNotesTables" roleURI="http://www.protalix.com/role/DisclosureConvertibleNotesTables" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureFairValueMeasurementTables" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementTables" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureSignificantAccountingPoliciesScheduleOfUsefulLifeDetails" roleURI="http://www.protalix.com/role/DisclosureSignificantAccountingPoliciesScheduleOfUsefulLifeDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureSignificantAccountingPoliciesAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureSignificantAccountingPoliciesAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureCommercializationAgreementsDetails" roleURI="http://www.protalix.com/role/DisclosureCommercializationAgreementsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosurePropertyAndEquipmentScheduleOfPropertyAndEquipmentDetails" roleURI="http://www.protalix.com/role/DisclosurePropertyAndEquipmentScheduleOfPropertyAndEquipmentDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureLiabilityForEmployeeRightsUponRetirementDetails" roleURI="http://www.protalix.com/role/DisclosureLiabilityForEmployeeRightsUponRetirementDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureCommitmentsDetails" roleURI="http://www.protalix.com/role/DisclosureCommitmentsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureOperatingLeasesAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureOperatingLeasesAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureRevenueDetails" roleURI="http://www.protalix.com/role/DisclosureRevenueDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalScheduleOfOptionsAndRestrictedStocksGrantedDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalScheduleOfOptionsAndRestrictedStocksGrantedDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalSummaryOfStockOptionActivityDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfStockOptionActivityDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalSummaryOfRestrictedStockActivityDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfRestrictedStockActivityDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalSummaryOfOptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfOptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalSummaryOfShareOptionsOutstandingAndExercisableDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfShareOptionsOutstandingAndExercisableDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalScheduleOfStockBasedCompensationExpenseInStatementOfOperationsDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalScheduleOfStockBasedCompensationExpenseInStatementOfOperationsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureShareCapitalAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureShareCapitalAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureConvertibleNotesScheduleOfFairValueAssumptionsDetails" roleURI="http://www.protalix.com/role/DisclosureConvertibleNotesScheduleOfFairValueAssumptionsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureConvertibleNotesScheduleOfInterestExpenseRecognizedDetails" roleURI="http://www.protalix.com/role/DisclosureConvertibleNotesScheduleOfInterestExpenseRecognizedDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureConvertibleNotesAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureConvertibleNotesAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureFairValueMeasurementScheduleOfFairValueAssumptionsDetails" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementScheduleOfFairValueAssumptionsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureFairValueMeasurementAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureTaxesOnIncomeScheduleOfOpenTaxYearsDetails" roleURI="http://www.protalix.com/role/DisclosureTaxesOnIncomeScheduleOfOpenTaxYearsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureTaxesOnIncomeAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureTaxesOnIncomeAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureRelatedPartyTransactionsDetails" roleURI="http://www.protalix.com/role/DisclosureRelatedPartyTransactionsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20211231.xsd#DisclosureSubsequentEventsDetails" roleURI="http://www.protalix.com/role/DisclosureSubsequentEventsDetails" />
  <link:arcroleRef arcroleURI="http://www.esma.europa.eu/xbrl/esef/arcrole/wider-narrower" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/arcrole/esma-arcrole-2018-11-21.xsd#wider-narrower" />
  <link:roleRef roleURI="http://www.protalix.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:href="plx-20211231.xsd#DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="simple" />
  <link:roleRef xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-roles-2021-01-31.xsd#eedm" roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" />
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended" xlink:title="Extensible Enumeration Domain Members" />
  <link:definitionLink xlink:role="http://www.protalix.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="extended" xlink:title="99900 - Disclosure - Standard And Custom Axis Domain Defaults">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="us-gaap_StatementClassOfStockAxis_1" xlink:title="us-gaap_StatementClassOfStockAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:label="us-gaap_ClassOfStockDomain_1" xlink:title="us-gaap_ClassOfStockDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_StatementClassOfStockAxis_1" xlink:to="us-gaap_ClassOfStockDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_StatementClassOfStockAxis_1 To us-gaap_ClassOfStockDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis_1" xlink:title="srt_ProductOrServiceAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain_1" xlink:title="srt_ProductsAndServicesDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_ProductOrServiceAxis_1" xlink:to="srt_ProductsAndServicesDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_ProductOrServiceAxis_1 To srt_ProductsAndServicesDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis_1" xlink:title="us-gaap_IncomeStatementLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_1" xlink:title="us-gaap_IncomeStatementLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeStatementLocationAxis_1" xlink:to="us-gaap_IncomeStatementLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeStatementLocationAxis_1 To us-gaap_IncomeStatementLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis_1" xlink:title="us-gaap_StatementEquityComponentsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_1" xlink:title="us-gaap_EquityComponentDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_StatementEquityComponentsAxis_1" xlink:to="us-gaap_EquityComponentDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_StatementEquityComponentsAxis_1 To us-gaap_EquityComponentDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis_1" xlink:title="us-gaap_AwardTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" xlink:title="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AwardTypeAxis_1" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AwardTypeAxis_1 To us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis_1" xlink:title="us-gaap_DebtInstrumentAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain_1" xlink:title="us-gaap_DebtInstrumentNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_DebtInstrumentAxis_1" xlink:to="us-gaap_DebtInstrumentNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_DebtInstrumentAxis_1 To us-gaap_DebtInstrumentNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis_1" xlink:title="us-gaap_TypeOfArrangementAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" xlink:title="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_TypeOfArrangementAxis_1" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_TypeOfArrangementAxis_1 To us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis_1" xlink:title="dei_LegalEntityAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain_1" xlink:title="dei_EntityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="dei_LegalEntityAxis_1" xlink:to="dei_EntityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:dei_LegalEntityAxis_1 To dei_EntityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis_1" xlink:title="srt_StatementGeographicalAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain_1" xlink:title="srt_SegmentGeographicalDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_StatementGeographicalAxis_1" xlink:to="srt_SegmentGeographicalDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_StatementGeographicalAxis_1 To srt_SegmentGeographicalDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis_1" xlink:title="srt_RangeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember_1" xlink:title="srt_RangeMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_RangeAxis_1" xlink:to="srt_RangeMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_RangeAxis_1 To srt_RangeMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:title="us-gaap_SubsidiarySaleOfStockAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_1" xlink:title="us-gaap_SaleOfStockNameOfTransactionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsidiarySaleOfStockAxis_1 To us-gaap_SaleOfStockNameOfTransactionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis_1" xlink:title="us-gaap_SubsequentEventTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_1" xlink:title="us-gaap_SubsequentEventTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsequentEventTypeAxis_1" xlink:to="us-gaap_SubsequentEventTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsequentEventTypeAxis_1 To us-gaap_SubsequentEventTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis_1" xlink:title="srt_CounterpartyNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain_1" xlink:title="srt_RepurchaseAgreementCounterpartyNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_CounterpartyNameAxis_1" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_CounterpartyNameAxis_1 To srt_RepurchaseAgreementCounterpartyNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementScenarioAxis" xlink:label="srt_StatementScenarioAxis_1" xlink:title="srt_StatementScenarioAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="srt_ScenarioUnspecifiedDomain_1" xlink:title="srt_ScenarioUnspecifiedDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_StatementScenarioAxis_1" xlink:to="srt_ScenarioUnspecifiedDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_StatementScenarioAxis_1 To srt_ScenarioUnspecifiedDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtTypeAxis" xlink:label="us-gaap_ShortTermDebtTypeAxis_1" xlink:title="us-gaap_ShortTermDebtTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtTypeDomain" xlink:label="us-gaap_ShortTermDebtTypeDomain_1" xlink:title="us-gaap_ShortTermDebtTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ShortTermDebtTypeAxis_1" xlink:to="us-gaap_ShortTermDebtTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ShortTermDebtTypeAxis_1 To us-gaap_ShortTermDebtTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:title="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" xlink:title="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByFairValueHierarchyLevelAxis_1 To us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeAxis" xlink:label="us-gaap_MeasurementInputTypeAxis_1" xlink:title="us-gaap_MeasurementInputTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain_1" xlink:title="us-gaap_MeasurementInputTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_MeasurementInputTypeAxis_1" xlink:to="us-gaap_MeasurementInputTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_MeasurementInputTypeAxis_1 To us-gaap_MeasurementInputTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodAxis" xlink:label="us-gaap_DebtInstrumentRedemptionPeriodAxis_1" xlink:title="us-gaap_DebtInstrumentRedemptionPeriodAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain" xlink:label="us-gaap_DebtInstrumentRedemptionPeriodDomain_1" xlink:title="us-gaap_DebtInstrumentRedemptionPeriodDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_DebtInstrumentRedemptionPeriodAxis_1" xlink:to="us-gaap_DebtInstrumentRedemptionPeriodDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_DebtInstrumentRedemptionPeriodAxis_1 To us-gaap_DebtInstrumentRedemptionPeriodDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingEstimateByTypeAxis" xlink:label="us-gaap_ChangeInAccountingEstimateByTypeAxis_1" xlink:title="us-gaap_ChangeInAccountingEstimateByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingEstimateTypeDomain" xlink:label="us-gaap_ChangeInAccountingEstimateTypeDomain_1" xlink:title="us-gaap_ChangeInAccountingEstimateTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ChangeInAccountingEstimateByTypeAxis_1" xlink:to="us-gaap_ChangeInAccountingEstimateTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ChangeInAccountingEstimateByTypeAxis_1 To us-gaap_ChangeInAccountingEstimateTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis_1" xlink:title="srt_TitleOfIndividualAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" xlink:title="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_TitleOfIndividualAxis_1" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_TitleOfIndividualAxis_1 To srt_TitleOfIndividualWithRelationshipToEntityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusAxis" xlink:label="us-gaap_GranteeStatusAxis_1" xlink:title="us-gaap_GranteeStatusAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusDomain" xlink:label="us-gaap_GranteeStatusDomain_1" xlink:title="us-gaap_GranteeStatusDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_GranteeStatusAxis_1" xlink:to="us-gaap_GranteeStatusDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_GranteeStatusAxis_1 To us-gaap_GranteeStatusDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis_1" xlink:title="us-gaap_PlanNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain_1" xlink:title="us-gaap_PlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PlanNameAxis_1" xlink:to="us-gaap_PlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PlanNameAxis_1 To us-gaap_PlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" xlink:title="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PropertyPlantAndEquipmentByTypeAxis_1 To us-gaap_PropertyPlantAndEquipmentTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" xlink:title="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember_1" xlink:title="us-gaap_TypeOfAdoptionMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" xlink:to="us-gaap_TypeOfAdoptionMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1 To us-gaap_TypeOfAdoptionMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeAxis" xlink:label="us-gaap_RetirementPlanTypeAxis_1" xlink:title="us-gaap_RetirementPlanTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeDomain" xlink:label="us-gaap_RetirementPlanTypeDomain_1" xlink:title="us-gaap_RetirementPlanTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_RetirementPlanTypeAxis_1" xlink:to="us-gaap_RetirementPlanTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_RetirementPlanTypeAxis_1 To us-gaap_RetirementPlanTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis_1" xlink:title="us-gaap_LongtermDebtTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain_1" xlink:title="us-gaap_LongtermDebtTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_LongtermDebtTypeAxis_1" xlink:to="us-gaap_LongtermDebtTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_LongtermDebtTypeAxis_1 To us-gaap_LongtermDebtTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1" xlink:title="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1" xlink:title="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1 To us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" xlink:title="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" xlink:title="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1 To us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis" xlink:label="us-gaap_ClassOfWarrantOrRightAxis_1" xlink:title="us-gaap_ClassOfWarrantOrRightAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain_1" xlink:title="us-gaap_ClassOfWarrantOrRightDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ClassOfWarrantOrRightAxis_1" xlink:to="us-gaap_ClassOfWarrantOrRightDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ClassOfWarrantOrRightAxis_1 To us-gaap_ClassOfWarrantOrRightDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:title="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain_1" xlink:title="us-gaap_RelatedPartyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:to="us-gaap_RelatedPartyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1 To us-gaap_RelatedPartyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:label="us-gaap_IncomeTaxAuthorityAxis_1" xlink:title="us-gaap_IncomeTaxAuthorityAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:label="us-gaap_IncomeTaxAuthorityDomain_1" xlink:title="us-gaap_IncomeTaxAuthorityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeTaxAuthorityAxis_1" xlink:to="us-gaap_IncomeTaxAuthorityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeTaxAuthorityAxis_1 To us-gaap_IncomeTaxAuthorityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="srt_ConsolidatedEntitiesAxis_1" xlink:title="srt_ConsolidatedEntitiesAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="srt_ConsolidatedEntitiesDomain_1" xlink:title="srt_ConsolidatedEntitiesDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_ConsolidatedEntitiesAxis_1" xlink:to="srt_ConsolidatedEntitiesDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_ConsolidatedEntitiesAxis_1 To srt_ConsolidatedEntitiesDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis_1" xlink:title="us-gaap_BalanceSheetLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain_1" xlink:title="us-gaap_BalanceSheetLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_BalanceSheetLocationAxis_1" xlink:to="us-gaap_BalanceSheetLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_BalanceSheetLocationAxis_1 To us-gaap_BalanceSheetLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="srt_MajorCustomersAxis_1" xlink:title="srt_MajorCustomersAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain_1" xlink:title="srt_NameOfMajorCustomerDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_MajorCustomersAxis_1" xlink:to="srt_NameOfMajorCustomerDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_MajorCustomersAxis_1 To srt_NameOfMajorCustomerDomain_1" order="1" />
  </link:definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/StatementConsolidatedStatementsOfOperations" xlink:type="extended" xlink:title="00200 - Statement - CONSOLIDATED STATEMENTS OF OPERATIONS">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LicenseAndServiceMember" xlink:label="us-gaap_LicenseAndServiceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_LicenseAndServiceMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues" xlink:label="us-gaap_Revenues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_Revenues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfRevenue" xlink:label="us-gaap_CostOfRevenue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CostOfRevenue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ResearchAndDevelopmentExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingExpense" xlink:label="us-gaap_OtherNonoperatingExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherNonoperatingExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncome" xlink:label="us-gaap_OtherNonoperatingIncome" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherNonoperatingIncome" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NonoperatingIncomeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="us-gaap_EarningsPerShareBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="us-gaap_EarningsPerShareDiluted" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareDiluted" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/StatementConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" xlink:type="extended" xlink:title="00300 - Statement - CONSOLIDATED STATEMENTS OF CHANGES IN STOCKHOLDERS' EQUITY (CAPITAL DEFICIENCY)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="us-gaap_AdditionalPaidInCapitalMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AdditionalPaidInCapitalMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="us-gaap_RetainedEarningsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_RetainedEarningsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquity" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesOutstanding" xlink:label="us-gaap_SharesOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharesOutstanding" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostValue" xlink:label="plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostInShares" xlink:label="plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostInShares" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostValue" xlink:to="plx_IssuanceOfCommonStockAndWarrantsNetOfIssuanceCostInShares" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodValueSalesAgreement" xlink:label="plx_StockIssuedDuringPeriodValueSalesAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_StockIssuedDuringPeriodValueSalesAgreement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodSharesSalesAgreement" xlink:label="plx_StockIssuedDuringPeriodSharesSalesAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_StockIssuedDuringPeriodValueSalesAgreement" xlink:to="plx_StockIssuedDuringPeriodSharesSalesAgreement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" xlink:label="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeituresShares" xlink:label="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeituresShares" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" xlink:to="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeituresShares" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodValueWarrantsExercises" xlink:label="plx_StockIssuedDuringPeriodValueWarrantsExercises" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_StockIssuedDuringPeriodValueWarrantsExercises" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodSharesWarrantsExercises" xlink:label="plx_StockIssuedDuringPeriodSharesWarrantsExercises" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_StockIssuedDuringPeriodValueWarrantsExercises" xlink:to="plx_StockIssuedDuringPeriodSharesWarrantsExercises" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ReacquisitionOfEquityComponentOfConvertibleNotes" xlink:label="plx_ReacquisitionOfEquityComponentOfConvertibleNotes" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ReacquisitionOfEquityComponentOfConvertibleNotes" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" xlink:label="plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureConvertibleNotesTables" xlink:type="extended" xlink:title="31003 - Disclosure - CONVERTIBLE NOTES (Tables)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ConvertibleNotesDue2021And2024Member" xlink:label="plx_ConvertibleNotesDue2021And2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_ConvertibleNotesDue2021And2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestIncomeAndInterestExpenseDisclosureTableTextBlock" xlink:label="us-gaap_InterestIncomeAndInterestExpenseDisclosureTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InterestIncomeAndInterestExpenseDisclosureTableTextBlock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureFairValueMeasurementTables" xlink:type="extended" xlink:title="31103 - Disclosure - FAIR VALUE MEASUREMENT (Tables)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ConvertibleNotesDue2021And2024Member" xlink:label="plx_ConvertibleNotesDue2021And2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_ConvertibleNotesDue2021And2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTableTextBlock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureSignificantAccountingPoliciesScheduleOfUsefulLifeDetails" xlink:type="extended" xlink:title="40101 - Disclosure - SIGNIFICANT ACCOUNTING POLICIES (Schedule of Useful Life) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:label="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_LaboratoryEquipmentMember" xlink:label="plx_LaboratoryEquipmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="plx_LaboratoryEquipmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember" xlink:label="us-gaap_FurnitureAndFixturesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_FurnitureAndFixturesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember" xlink:label="us-gaap_ComputerEquipmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_ComputerEquipmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems" xlink:label="us-gaap_PropertyPlantAndEquipmentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife" xlink:label="us-gaap_PropertyPlantAndEquipmentUsefulLife" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentUsefulLife" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureSignificantAccountingPoliciesAdditionalInformationDetails" xlink:type="extended" xlink:title="40102 - Disclosure - SIGNIFICANT ACCOUNTING POLICIES (Additional Information) (Details)">
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SignificantAccountingPoliciesTable" xlink:label="plx_SignificantAccountingPoliciesTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AtMarketEquityOfferingMember" xlink:label="plx_AtMarketEquityOfferingMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="plx_AtMarketEquityOfferingMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrivatePlacementMember" xlink:label="us-gaap_PrivatePlacementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_PrivatePlacementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AmendedPfizerAgreementMember" xlink:label="plx_AmendedPfizerAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_AmendedPfizerAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:label="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiUSAgreementMember" xlink:label="plx_ChiesiUSAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:to="plx_ChiesiUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiExUSAgreementMember" xlink:label="plx_ChiesiExUSAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:to="plx_ChiesiExUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="dei_LegalEntityAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ProtalixBioTherapeuticsIncorporationMember" xlink:label="plx_ProtalixBioTherapeuticsIncorporationMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="dei_EntityDomain" xlink:to="plx_ProtalixBioTherapeuticsIncorporationMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="srt_StatementGeographicalAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_BR" xlink:label="country_BR" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_BR" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="6" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ConvertibleNotesDue2021And2024Member" xlink:label="plx_ConvertibleNotesDue2021And2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_ConvertibleNotesDue2021And2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="srt_MajorCustomersAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="7" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="srt_MajorCustomersAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_FiocruzMember" xlink:label="plx_FiocruzMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="plx_FiocruzMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiMember" xlink:label="plx_ChiesiMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="plx_ChiesiMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SignificantAccountingPoliciesLineItems" xlink:label="plx_SignificantAccountingPoliciesLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_SignificantAccountingPoliciesTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:label="us-gaap_SharesIssuedPricePerShare" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharePrice" xlink:label="us-gaap_SharePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_SharePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SaleOfStockMaximumOfferingPrice" xlink:label="plx_SaleOfStockMaximumOfferingPrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_SaleOfStockMaximumOfferingPrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" xlink:label="plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:label="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_WarrantsAndRightsCommencementPeriodForExerciseOfWarrants" xlink:label="plx_WarrantsAndRightsCommencementPeriodForExerciseOfWarrants" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_WarrantsAndRightsCommencementPeriodForExerciseOfWarrants" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WarrantsAndRightsOutstandingTerm" xlink:label="us-gaap_WarrantsAndRightsOutstandingTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_WarrantsAndRightsOutstandingTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfPrivatePlacement" xlink:label="us-gaap_ProceedsFromIssuanceOfPrivatePlacement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfPrivatePlacement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_UpfrontNonrefundableNoncreditablePaymentReceivable" xlink:label="plx_UpfrontNonrefundableNoncreditablePaymentReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_UpfrontNonrefundableNoncreditablePaymentReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AdditionalAmountsPayableToCoverDevelopmentCosts" xlink:label="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PaymentOnNetSalesPercentage" xlink:label="plx_PaymentOnNetSalesPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_PaymentOnNetSalesPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" xlink:label="plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebt" xlink:label="us-gaap_ConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_TaxRateAssumptionRelatedToDeferredTaxDifferenceReversal" xlink:label="plx_TaxRateAssumptionRelatedToDeferredTaxDifferenceReversal" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="20" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_TaxRateAssumptionRelatedToDeferredTaxDifferenceReversal" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="21" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="22" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="23" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_OperatingLeaseLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_RevenuePerformanceObligationNumber" xlink:label="plx_RevenuePerformanceObligationNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="24" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_RevenuePerformanceObligationNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="25" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_AccountsReceivableNetCurrent" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureCommercializationAgreementsDetails" xlink:type="extended" xlink:title="40201 - Disclosure - COMMERCIALIZATION AGREEMENTS (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PfizerMember" xlink:label="plx_PfizerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_PfizerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:label="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiUSAgreementMember" xlink:label="plx_ChiesiUSAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:to="plx_ChiesiUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiExUSAgreementMember" xlink:label="plx_ChiesiExUSAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:to="plx_ChiesiExUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_KirinHoldingsCompanyLimitedMember" xlink:label="plx_KirinHoldingsCompanyLimitedMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_KirinHoldingsCompanyLimitedMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_StatementTable" xlink:to="srt_StatementGeographicalAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_BR" xlink:label="country_BR" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_BR" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CollaborativeArrangementProfitSharePercentage" xlink:label="plx_CollaborativeArrangementProfitSharePercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_CollaborativeArrangementProfitSharePercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NotesPayableCurrent" xlink:label="us-gaap_NotesPayableCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NotesPayableCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromRepaymentsOfNotesPayable" xlink:label="us-gaap_ProceedsFromRepaymentsOfNotesPayable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromRepaymentsOfNotesPayable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_UpfrontNonrefundableNoncreditablePaymentReceivable" xlink:label="plx_UpfrontNonrefundableNoncreditablePaymentReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_UpfrontNonrefundableNoncreditablePaymentReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AdditionalAmountsPayableToCoverDevelopmentCosts" xlink:label="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" xlink:label="plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AgreementAmendmentPaymentReceivable" xlink:label="plx_AgreementAmendmentPaymentReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_AgreementAmendmentPaymentReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" xlink:label="plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" xlink:label="plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PaymentOnNetSalesPercentage" xlink:label="plx_PaymentOnNetSalesPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PaymentOnNetSalesPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PaymentInConsiderationForDevelopmentServicesPerformed" xlink:label="plx_PaymentInConsiderationForDevelopmentServicesPerformed" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PaymentInConsiderationForDevelopmentServicesPerformed" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PaymentsInConnectionWithPerformanceOfAdditionalStudies" xlink:label="plx_PaymentsInConnectionWithPerformanceOfAdditionalStudies" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PaymentsInConnectionWithPerformanceOfAdditionalStudies" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ContractWithCustomerLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_NonRefundableFutureServicePayment" xlink:label="plx_NonRefundableFutureServicePayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_NonRefundableFutureServicePayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfAdultGaucherPatientsTreatedWithAlfataliglicerase" xlink:label="plx_PercentageOfAdultGaucherPatientsTreatedWithAlfataliglicerase" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PercentageOfAdultGaucherPatientsTreatedWithAlfataliglicerase" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfNotesPayable" xlink:label="us-gaap_RepaymentsOfNotesPayable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RepaymentsOfNotesPayable" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosurePropertyAndEquipmentScheduleOfPropertyAndEquipmentDetails" xlink:type="extended" xlink:title="40301 - Disclosure - PROPERTY AND EQUIPMENT (Schedule of Property and Equipment) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:label="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_LaboratoryEquipmentMember" xlink:label="plx_LaboratoryEquipmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="plx_LaboratoryEquipmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_FurnitureAndComputerEquipmentMember" xlink:label="plx_FurnitureAndComputerEquipmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="plx_FurnitureAndComputerEquipmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseholdImprovementsMember" xlink:label="us-gaap_LeaseholdImprovementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_LeaseholdImprovementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems" xlink:label="us-gaap_PropertyPlantAndEquipmentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="us-gaap_PropertyPlantAndEquipmentGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureLiabilityForEmployeeRightsUponRetirementDetails" xlink:type="extended" xlink:title="40501 - Disclosure - LIABILITY FOR EMPLOYEE RIGHTS UPON RETIREMENT (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeAxis" xlink:label="us-gaap_RetirementPlanTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_RetirementPlanTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeDomain" xlink:label="us-gaap_RetirementPlanTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RetirementPlanTypeAxis" xlink:to="us-gaap_RetirementPlanTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPostretirementLifeInsuranceMember" xlink:label="us-gaap_DefinedBenefitPostretirementLifeInsuranceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RetirementPlanTypeDomain" xlink:to="us-gaap_DefinedBenefitPostretirementLifeInsuranceMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ContributionPlansMember" xlink:label="plx_ContributionPlansMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RetirementPlanTypeDomain" xlink:to="plx_ContributionPlansMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EmployeeSeveranceObligationPayment" xlink:label="plx_EmployeeSeveranceObligationPayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_EmployeeSeveranceObligationPayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PostemploymentBenefitsPeriodExpense" xlink:label="us-gaap_PostemploymentBenefitsPeriodExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PostemploymentBenefitsPeriodExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount" xlink:label="us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanAmountsRecognizedInOtherComprehensiveIncomeLossNetGainLossBeforeTax" xlink:label="us-gaap_DefinedBenefitPlanAmountsRecognizedInOtherComprehensiveIncomeLossNetGainLossBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DefinedBenefitPlanAmountsRecognizedInOtherComprehensiveIncomeLossNetGainLossBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanExpectedFutureEmployerContributionsNextFiscalYear" xlink:label="us-gaap_DefinedBenefitPlanExpectedFutureEmployerContributionsNextFiscalYear" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DefinedBenefitPlanExpectedFutureEmployerContributionsNextFiscalYear" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_NumberOfEmployeesToReceiveBenefitsDuringNextFiveYears" xlink:label="plx_NumberOfEmployeesToReceiveBenefitsDuringNextFiveYears" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_NumberOfEmployeesToReceiveBenefitsDuringNextFiveYears" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_BenefitsPayableDuringNextFiveYears" xlink:label="plx_BenefitsPayableDuringNextFiveYears" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_BenefitsPayableDuringNextFiveYears" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureCommitmentsDetails" xlink:type="extended" xlink:title="40601 - Disclosure - COMMITMENTS (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:label="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RoyaltyAgreementTermsMember" xlink:label="us-gaap_RoyaltyAgreementTermsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="us-gaap_RoyaltyAgreementTermsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_OfficeOfIsraeliInnovationAuthorityMember" xlink:label="plx_OfficeOfIsraeliInnovationAuthorityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="plx_OfficeOfIsraeliInnovationAuthorityMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_OutsideOfIsraelMember" xlink:label="plx_OutsideOfIsraelMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_OfficeOfIsraeliInnovationAuthorityMember" xlink:to="plx_OutsideOfIsraelMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NoncollaborativeArrangementTransactionsMember" xlink:label="us-gaap_NoncollaborativeArrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_NoncollaborativeArrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CommitmentsAndContingenciesLineItems" xlink:label="plx_CommitmentsAndContingenciesLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_RoyaltiesOnSaleOfProducts" xlink:label="plx_RoyaltiesOnSaleOfProducts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="plx_RoyaltiesOnSaleOfProducts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RoyaltyExpense" xlink:label="us-gaap_RoyaltyExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="us-gaap_RoyaltyExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedRoyaltiesCurrentAndNoncurrent" xlink:label="us-gaap_AccruedRoyaltiesCurrentAndNoncurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="us-gaap_AccruedRoyaltiesCurrentAndNoncurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CommitmentAmount" xlink:label="plx_CommitmentAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="plx_CommitmentAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfRoyaltiesToGrantReceived" xlink:label="plx_PercentageOfRoyaltiesToGrantReceived" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="plx_CommitmentsAndContingenciesLineItems" xlink:to="plx_PercentageOfRoyaltiesToGrantReceived" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureOperatingLeasesAdditionalInformationDetails" xlink:type="extended" xlink:title="40703 - Disclosure - OPERATING LEASES (Additional Information) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="us-gaap_LesseeLeaseDescriptionTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VehiclesMember" xlink:label="us-gaap_VehiclesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_VehiclesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DisclosureOfLeasesOperatingLineItems" xlink:label="plx_DisclosureOfLeasesOperatingLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseOptionToExtend" xlink:label="us-gaap_LesseeOperatingLeaseOptionToExtend" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="us-gaap_LesseeOperatingLeaseOptionToExtend" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_LesseeOperatingLeaseNumberOfRenewalTermExtensions" xlink:label="plx_LesseeOperatingLeaseNumberOfRenewalTermExtensions" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="plx_LesseeOperatingLeaseNumberOfRenewalTermExtensions" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecurityDeposit" xlink:label="us-gaap_SecurityDeposit" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="us-gaap_SecurityDeposit" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfChangeInOperatingLeaseMonthlyRentalPayments" xlink:label="plx_PercentageOfChangeInOperatingLeaseMonthlyRentalPayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="plx_DisclosureOfLeasesOperatingLineItems" xlink:to="plx_PercentageOfChangeInOperatingLeaseMonthlyRentalPayments" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureRevenueDetails" xlink:type="extended" xlink:title="40801 - Disclosure - REVENUE (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LicenseAndServiceMember" xlink:label="us-gaap_LicenseAndServiceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_LicenseAndServiceMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="srt_StatementGeographicalAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PfizerMember" xlink:label="plx_PfizerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_SegmentGeographicalDomain" xlink:to="plx_PfizerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_BR" xlink:label="country_BR" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_BR" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiMember" xlink:label="plx_ChiesiMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_SegmentGeographicalDomain" xlink:to="plx_ChiesiMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues" xlink:label="us-gaap_Revenues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_Revenues" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalScheduleOfOptionsAndRestrictedStocksGrantedDetails" xlink:type="extended" xlink:title="40901 - Disclosure - SHARE CAPITAL (Schedule of Options and Restricted Stocks Granted) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice4.69Member" xlink:label="plx_ExercisePrice4.69Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice4.69Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice2.00Member" xlink:label="plx_ExercisePrice2.00Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice2.00Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.59OneMember" xlink:label="plx_ExercisePrice3.59OneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.59OneMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.66Member" xlink:label="plx_ExercisePrice3.66Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.66Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.73Member" xlink:label="plx_ExercisePrice3.73Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.73Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_NoExercisePriceMember" xlink:label="plx_NoExercisePriceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_NoExercisePriceMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.59TwoMember" xlink:label="plx_ExercisePrice3.59TwoMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.59TwoMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice1.57Member" xlink:label="plx_ExercisePrice1.57Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice1.57Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" xlink:label="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantedContractualTerm" xlink:label="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantedContractualTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantedContractualTerm" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfStockOptionActivityDetails" xlink:type="extended" xlink:title="40902 - Disclosure - SHARE CAPITAL (Summary of Stock Option Activity) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_TitleOfIndividualAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_TitleOfIndividualAxis" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EmployeeMember" xlink:label="plx_EmployeeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_EmployeeMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfRestrictedStockActivityDetails" xlink:type="extended" xlink:title="40903 - Disclosure - SHARE CAPITAL (Summary of Restricted Stock Activity) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_TitleOfIndividualAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_TitleOfIndividualAxis" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EmployeeMember" xlink:label="plx_EmployeeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_EmployeeMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfOptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersDetails" xlink:type="extended" xlink:title="40904 - Disclosure - SHARE CAPITAL (Summary of Options Granted to Consultants, Directors, and Other Service Providers) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_TitleOfIndividualAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_TitleOfIndividualAxis" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_OptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersMember" xlink:label="plx_OptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_OptionsGrantedToConsultantsDirectorsAndOtherServiceProvidersMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodSharesStockExpired" xlink:label="plx_StockIssuedDuringPeriodSharesStockExpired" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="plx_StockIssuedDuringPeriodSharesStockExpired" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalSummaryOfShareOptionsOutstandingAndExercisableDetails" xlink:type="extended" xlink:title="40905 - Disclosure - SHARE CAPITAL (Summary of Share Options Outstanding and Exercisable) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice1.57Member" xlink:label="plx_ExercisePrice1.57Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice1.57Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice2.00Member" xlink:label="plx_ExercisePrice2.00Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice2.00Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.55Member" xlink:label="plx_ExercisePrice3.55Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.55Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.59Member" xlink:label="plx_ExercisePrice3.59Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.59Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.66Member" xlink:label="plx_ExercisePrice3.66Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.66Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.70Member" xlink:label="plx_ExercisePrice3.70Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.70Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice3.73Member" xlink:label="plx_ExercisePrice3.73Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice3.73Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice4.69Member" xlink:label="plx_ExercisePrice4.69Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice4.69Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice5.10Member" xlink:label="plx_ExercisePrice5.10Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice5.10Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice5.60Member" xlink:label="plx_ExercisePrice5.60Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice5.60Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ExercisePrice17.20Member" xlink:label="plx_ExercisePrice17.20Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="plx_ExercisePrice17.20Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2" xlink:label="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageRemainingContractualTerm2" xlink:label="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageRemainingContractualTerm2" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageRemainingContractualTerm2" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalScheduleOfStockBasedCompensationExpenseInStatementOfOperationsDetails" xlink:type="extended" xlink:title="40906 - Disclosure - SHARE CAPITAL (Schedule of Stock-Based Compensation Expense in Statement of Operations) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="us-gaap_CostOfSalesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_CostOfSalesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureShareCapitalAdditionalInformationDetails" xlink:type="extended" xlink:title="40907 - Disclosure - SHARE CAPITAL (Additional information) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_TitleOfIndividualAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_TitleOfIndividualAxis" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PresidentAndChiefExecutiveOfficerMember" xlink:label="plx_PresidentAndChiefExecutiveOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_PresidentAndChiefExecutiveOfficerMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SeniorVicePresidentAndChiefDevelopmentOfficerMember" xlink:label="plx_SeniorVicePresidentAndChiefDevelopmentOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_SeniorVicePresidentAndChiefDevelopmentOfficerMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SeniorVicePresidentAndChiefFinancialOfficerMember" xlink:label="plx_SeniorVicePresidentAndChiefFinancialOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_SeniorVicePresidentAndChiefFinancialOfficerMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SeniorVicePresidentOperationsMember" xlink:label="plx_SeniorVicePresidentOperationsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_SeniorVicePresidentOperationsMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_VicePresidentResearchAndDevelopmentMember" xlink:label="plx_VicePresidentResearchAndDevelopmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_VicePresidentResearchAndDevelopmentMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ChiefExecutiveOfficerMember" xlink:label="srt_ChiefExecutiveOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="srt_ChiefExecutiveOfficerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ChiefFinancialOfficerMember" xlink:label="srt_ChiefFinancialOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="srt_ChiefFinancialOfficerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CertainEmployeesMember" xlink:label="plx_CertainEmployeesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_CertainEmployeesMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_BoardOfDirectorsChairmanMember" xlink:label="srt_BoardOfDirectorsChairmanMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="srt_BoardOfDirectorsChairmanMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrivatePlacementMember" xlink:label="us-gaap_PrivatePlacementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_PrivatePlacementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AtMarketEquityOfferingMember" xlink:label="plx_AtMarketEquityOfferingMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="plx_AtMarketEquityOfferingMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AtmEquityOfferingSalesAgreementMember" xlink:label="plx_AtmEquityOfferingSalesAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="plx_AtmEquityOfferingSalesAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OverAllotmentOptionMember" xlink:label="us-gaap_OverAllotmentOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_OverAllotmentOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_PlanNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EmployeeStockIncentivePlan2006Member" xlink:label="plx_EmployeeStockIncentivePlan2006Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PlanNameDomain" xlink:to="plx_EmployeeStockIncentivePlan2006Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CommonStockNumberOfVotingRights" xlink:label="plx_CommonStockNumberOfVotingRights" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_CommonStockNumberOfVotingRights" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" xlink:label="us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_NumberOfDirectors" xlink:label="plx_NumberOfDirectors" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_NumberOfDirectors" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedNumberOfShares" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedNumberOfShares" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedNumberOfShares" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsNonvestedNumberOfShares" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsNonvestedNumberOfShares" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsNonvestedNumberOfShares" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfQuarterlyIncrements" xlink:label="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfQuarterlyIncrements" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfQuarterlyIncrements" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" xlink:label="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardGrantDateFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsGrantsContingentUponCertainConditionsAggregateValue" xlink:label="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsGrantsContingentUponCertainConditionsAggregateValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="20" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsGrantsContingentUponCertainConditionsAggregateValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="21" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="22" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="23" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="24" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1" xlink:label="us-gaap_DebtConversionConvertedInstrumentSharesIssued1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="25" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_DebtConversionConvertedInstrumentSharesIssued1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfConvertibleDebt" xlink:label="us-gaap_RepaymentsOfConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="26" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_RepaymentsOfConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="27" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharePrice" xlink:label="us-gaap_SharePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="28" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" xlink:label="plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="29" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_StockIssuedDuringPeriodIssuePricePerShareNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfPrivatePlacement" xlink:label="us-gaap_ProceedsFromIssuanceOfPrivatePlacement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="30" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfPrivatePlacement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="31" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:label="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="32" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromWarrantExercises" xlink:label="us-gaap_ProceedsFromWarrantExercises" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="33" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ProceedsFromWarrantExercises" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="34" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SaleOfStockMaximumOfferingPrice" xlink:label="plx_SaleOfStockMaximumOfferingPrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="35" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_SaleOfStockMaximumOfferingPrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfCommissionOnSaleOfShares" xlink:label="plx_PercentageOfCommissionOnSaleOfShares" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="36" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_PercentageOfCommissionOnSaleOfShares" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureConvertibleNotesScheduleOfFairValueAssumptionsDetails" xlink:type="extended" xlink:title="41001 - Disclosure - CONVERTIBLE NOTES (Schedule of Fair Value Assumptions) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeAxis" xlink:label="us-gaap_MeasurementInputTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_MeasurementInputTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputSharePriceMember" xlink:label="us-gaap_MeasurementInputSharePriceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputSharePriceMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputExpectedTermMember" xlink:label="us-gaap_MeasurementInputExpectedTermMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputExpectedTermMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputRiskFreeInterestRateMember" xlink:label="us-gaap_MeasurementInputRiskFreeInterestRateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputRiskFreeInterestRateMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputPriceVolatilityMember" xlink:label="us-gaap_MeasurementInputPriceVolatilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputPriceVolatilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_MeasurementInputYieldMember" xlink:label="plx_MeasurementInputYieldMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="plx_MeasurementInputYieldMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentMeasurementInput" xlink:label="us-gaap_DebtInstrumentMeasurementInput" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentMeasurementInput" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureConvertibleNotesScheduleOfInterestExpenseRecognizedDetails" xlink:type="extended" xlink:title="41002 - Disclosure - CONVERTIBLE NOTES (Schedule of Interest Expense Recognized) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpenseDebtExcludingAmortization" xlink:label="us-gaap_InterestExpenseDebtExcludingAmortization" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InterestExpenseDebtExcludingAmortization" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium" xlink:label="us-gaap_AmortizationOfDebtDiscountPremium" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AmortizationOfDebtDiscountPremium" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts" xlink:label="us-gaap_AmortizationOfFinancingCostsAndDiscounts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AmortizationOfFinancingCostsAndDiscounts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_InterestExpenseDebtOther" xlink:label="plx_InterestExpenseDebtOther" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_InterestExpenseDebtOther" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestCostsIncurred" xlink:label="us-gaap_InterestCostsIncurred" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InterestCostsIncurred" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureConvertibleNotesAdditionalInformationDetails" xlink:type="extended" xlink:title="41003 - Disclosure - CONVERTIBLE NOTES (Additional Information) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_FourPointFivePercentageConvertibleNotesMember" xlink:label="plx_FourPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_FourPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ConvertibleNotesDueTwoThousandTwentyOneMember" xlink:label="plx_ConvertibleNotesDueTwoThousandTwentyOneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_ConvertibleNotesDueTwoThousandTwentyOneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="us-gaap_DebtInstrumentCarryingAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentCarryingAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfConvertibleDebt" xlink:label="us-gaap_RepaymentsOfConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RepaymentsOfConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtConversionConvertedInstrumentExchangeInCashAccruedAndUnpaidInterest" xlink:label="plx_DebtConversionConvertedInstrumentExchangeInCashAccruedAndUnpaidInterest" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtConversionConvertedInstrumentExchangeInCashAccruedAndUnpaidInterest" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtInstrumentConvertibleBaseValueForConversionRate" xlink:label="plx_DebtInstrumentConvertibleBaseValueForConversionRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtInstrumentConvertibleBaseValueForConversionRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="us-gaap_ProceedsFromConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtInstrumentConvertibleConversionShareNumber" xlink:label="plx_DebtInstrumentConvertibleConversionShareNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtInstrumentConvertibleConversionShareNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfPremiumToClosingPriceOfStock" xlink:label="plx_PercentageOfPremiumToClosingPriceOfStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PercentageOfPremiumToClosingPriceOfStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentTerm" xlink:label="us-gaap_DebtInstrumentTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ReacquisitionOfEquityComponentOfConvertibleNotes" xlink:label="plx_ReacquisitionOfEquityComponentOfConvertibleNotes" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ReacquisitionOfEquityComponentOfConvertibleNotes" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" xlink:label="plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_EquityComponentOfConvertibleNotesNetOfTransactionCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtConversionTransactionCostsInConnectionWithExchangeOfConvertibleDebt" xlink:label="plx_DebtConversionTransactionCostsInConnectionWithExchangeOfConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtConversionTransactionCostsInConnectionWithExchangeOfConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_MaintainOfMinimumCashBalance" xlink:label="plx_MaintainOfMinimumCashBalance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_MaintainOfMinimumCashBalance" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_MaximumDebtInstrumentConvertibleConversionShareNumber" xlink:label="plx_MaximumDebtInstrumentConvertibleConversionShareNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_MaximumDebtInstrumentConvertibleConversionShareNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebt" xlink:label="us-gaap_ConvertibleDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ConvertibleDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRedemptionDescription" xlink:label="us-gaap_DebtInstrumentRedemptionDescription" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="20" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentRedemptionDescription" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays" xlink:label="us-gaap_DebtInstrumentConvertibleThresholdTradingDays" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="21" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentConvertibleThresholdTradingDays" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1" xlink:label="us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="22" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ThresholdPercentageOfConversionPrice" xlink:label="plx_ThresholdPercentageOfConversionPrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="23" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ThresholdPercentageOfConversionPrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtInstrumentAggregatePercentageOfPrincipleAmountOutstanding" xlink:label="plx_DebtInstrumentAggregatePercentageOfPrincipleAmountOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="24" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtInstrumentAggregatePercentageOfPrincipleAmountOutstanding" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtInstrumentRedemption" xlink:label="plx_DebtInstrumentRedemption" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="25" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtInstrumentRedemption" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PercentageOfOutstandingCapitalStock" xlink:label="plx_PercentageOfOutstandingCapitalStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="26" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_PercentageOfOutstandingCapitalStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_DebtInstrumentPrincipalAmountDenominationForConversionIntoCommonStock" xlink:label="plx_DebtInstrumentPrincipalAmountDenominationForConversionIntoCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="27" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_DebtInstrumentPrincipalAmountDenominationForConversionIntoCommonStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_NumberOfCalendarDaysAfterDateOfApplicableFundamentalChange" xlink:label="plx_NumberOfCalendarDaysAfterDateOfApplicableFundamentalChange" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="28" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_NumberOfCalendarDaysAfterDateOfApplicableFundamentalChange" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed" xlink:label="us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="29" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1" xlink:label="us-gaap_DebtConversionConvertedInstrumentSharesIssued1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="30" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtConversionConvertedInstrumentSharesIssued1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureFairValueMeasurementScheduleOfFairValueAssumptionsDetails" xlink:type="extended" xlink:title="41101 - Disclosure - FAIR VALUE MEASUREMENT (Schedule of Fair Value Assumptions) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ConvertibleNotesDue2021And2024Member" xlink:label="plx_ConvertibleNotesDue2021And2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_ConvertibleNotesDue2021And2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="plx_ConvertibleNotesDue2021And2024Member" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeAxis" xlink:label="us-gaap_MeasurementInputTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:to="us-gaap_MeasurementInputTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputSharePriceMember" xlink:label="us-gaap_MeasurementInputSharePriceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputSharePriceMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputExpectedTermMember" xlink:label="us-gaap_MeasurementInputExpectedTermMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputExpectedTermMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputRiskFreeInterestRateMember" xlink:label="us-gaap_MeasurementInputRiskFreeInterestRateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputRiskFreeInterestRateMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MeasurementInputPriceVolatilityMember" xlink:label="us-gaap_MeasurementInputPriceVolatilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputPriceVolatilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_MeasurementInputYieldMember" xlink:label="plx_MeasurementInputYieldMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="plx_MeasurementInputYieldMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentMeasurementInput" xlink:label="us-gaap_DebtInstrumentMeasurementInput" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentMeasurementInput" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureFairValueMeasurementAdditionalInformationDetails" xlink:type="extended" xlink:title="41102 - Disclosure - FAIR VALUE MEASUREMENT (Additional Information) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageConvertibleNotesMember" xlink:label="plx_SevenPointFivePercentageConvertibleNotesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageConvertibleNotesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" xlink:label="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_SevenPointFivePercentageSeniorSecuredConvertibleNotesDue2024Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="us-gaap_DebtInstrumentCarryingAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentCarryingAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtFairValueDisclosures" xlink:label="us-gaap_ConvertibleDebtFairValueDisclosures" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ConvertibleDebtFairValueDisclosures" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureTaxesOnIncomeScheduleOfOpenTaxYearsDetails" xlink:type="extended" xlink:title="41202 - Disclosure - TAXES ON INCOME (Schedule of Open Tax Years) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxContingencyTable" xlink:label="us-gaap_IncomeTaxContingencyTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:label="us-gaap_IncomeTaxAuthorityAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="us-gaap_IncomeTaxAuthorityAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:label="us-gaap_IncomeTaxAuthorityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeTaxAuthorityAxis" xlink:to="us-gaap_IncomeTaxAuthorityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_UsIsraelMember" xlink:label="plx_UsIsraelMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeTaxAuthorityDomain" xlink:to="plx_UsIsraelMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_US" xlink:label="country_US" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeTaxAuthorityDomain" xlink:to="country_US" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxContingencyLineItems" xlink:label="us-gaap_IncomeTaxContingencyLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_IncomeTaxContingencyTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OpenTaxYear" xlink:label="us-gaap_OpenTaxYear" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_OpenTaxYear" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureTaxesOnIncomeAdditionalInformationDetails" xlink:type="extended" xlink:title="41203 - Disclosure - TAXES ON INCOME (Additional Information) (Details)">
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_IncomeTaxDisclosureTable" xlink:label="plx_IncomeTaxDisclosureTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="plx_IncomeTaxDisclosureTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="srt_ConsolidatedEntitiesAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="plx_IncomeTaxDisclosureTable" xlink:to="srt_ConsolidatedEntitiesAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="srt_ConsolidatedEntitiesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ConsolidatedEntitiesAxis" xlink:to="srt_ConsolidatedEntitiesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ParentCompanyMember" xlink:label="srt_ParentCompanyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ConsolidatedEntitiesDomain" xlink:to="srt_ParentCompanyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SubsidiariesMember" xlink:label="srt_SubsidiariesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ConsolidatedEntitiesDomain" xlink:to="srt_SubsidiariesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:label="us-gaap_IncomeTaxAuthorityAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="plx_IncomeTaxDisclosureTable" xlink:to="us-gaap_IncomeTaxAuthorityAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:label="us-gaap_IncomeTaxAuthorityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeTaxAuthorityAxis" xlink:to="us-gaap_IncomeTaxAuthorityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_TaxYearThereafterMember" xlink:label="plx_TaxYearThereafterMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeTaxAuthorityDomain" xlink:to="plx_TaxYearThereafterMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_IncomeTaxDisclosureLineItems" xlink:label="plx_IncomeTaxDisclosureLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="plx_IncomeTaxDisclosureLineItems" xlink:to="plx_IncomeTaxDisclosureTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_IncomeTaxDisclosureLineItems" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwards" xlink:label="us-gaap_OperatingLossCarryforwards" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="plx_IncomeTaxDisclosureLineItems" xlink:to="us-gaap_OperatingLossCarryforwards" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureRelatedPartyTransactionsDetails" xlink:type="extended" xlink:title="41401 - Disclosure - RELATED PARTY TRANSACTIONS (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:label="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_CompensationToNonExecutiveDirectorsMember" xlink:label="plx_CompensationToNonExecutiveDirectorsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="plx_CompensationToNonExecutiveDirectorsMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyTransactionLineItems" xlink:label="us-gaap_RelatedPartyTransactionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyTransactionAmountsOfTransaction" xlink:label="us-gaap_RelatedPartyTransactionAmountsOfTransaction" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="us-gaap_RelatedPartyTransactionAmountsOfTransaction" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureSubsequentEventsDetails" xlink:type="extended" xlink:title="41501 - Disclosure - SUBSEQUENT EVENTS (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTable" xlink:label="us-gaap_SubsequentEventTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_SubsequentEventTable" xlink:to="us-gaap_SubsequentEventTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="us-gaap_SubsequentEventMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_SubsequentEventTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ChiesiAgreementsMember" xlink:label="plx_ChiesiAgreementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiAgreementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SupplyAndTechnologyTransferAgreementWithFiocruzMember" xlink:label="plx_SupplyAndTechnologyTransferAgreementWithFiocruzMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_SupplyAndTechnologyTransferAgreementWithFiocruzMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_SubsequentEventTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_AlfataligliceraseMember" xlink:label="plx_AlfataligliceraseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="plx_AlfataligliceraseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_SubsequentEventTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="us-gaap_SubsequentEventTable" xlink:to="srt_TitleOfIndividualAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_TitleOfIndividualAxis" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_PresidentAndChiefExecutiveOfficerMember" xlink:label="plx_PresidentAndChiefExecutiveOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_PresidentAndChiefExecutiveOfficerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_SeniorVicePresidentAndChiefFinancialOfficerMember" xlink:label="plx_SeniorVicePresidentAndChiefFinancialOfficerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:to="plx_SeniorVicePresidentAndChiefFinancialOfficerMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventLineItems" xlink:label="us-gaap_SubsequentEventLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_SubsequentEventTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ProceedsFromExpenseReimbursements" xlink:label="plx_ProceedsFromExpenseReimbursements" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_ProceedsFromExpenseReimbursements" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20211231.xsd#plx_ProceedsFromSaleOfProducts" xlink:label="plx_ProceedsFromSaleOfProducts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_ProceedsFromSaleOfProducts" priority="1" use="optional" />
  </definitionLink>
</link:linkbase>
