<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  9.6.7811.37134 -->
<!--Based on XBRL 2.1-->
<!--Created on: 8/16/2021 11:17:11 AM-->
<!--Modified on: 8/16/2021 11:17:11 AM-->
<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">
  <roleRef xlink:type="simple" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-roles-2020-01-31.xsd#eedm" roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#StatementCondensedConsolidatedStatementsOfOperations" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfOperations" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#StatementCondensedConsolidatedStatementsOfOperationsParenthetical" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfOperationsParenthetical" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#StatementCondensedConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureFairValueMeasurementTables" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementTables" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureSignificantAccountingPoliciesDetails" roleURI="http://www.protalix.com/role/DisclosureSignificantAccountingPoliciesDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureFairValueMeasurementLiabilityComponentWasValuedBasedOnIncomeApproachDetails" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementLiabilityComponentWasValuedBasedOnIncomeApproachDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureFairValueMeasurementAdditionalInformationDetails" roleURI="http://www.protalix.com/role/DisclosureFairValueMeasurementAdditionalInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureRevenuesCompanySDisaggregationOfRevenuesDetails" roleURI="http://www.protalix.com/role/DisclosureRevenuesCompanySDisaggregationOfRevenuesDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureStockTransactionsDetails" roleURI="http://www.protalix.com/role/DisclosureStockTransactionsDetails" />
  <roleRef xlink:type="simple" xlink:href="plx-20210630.xsd#DisclosureSubsequentEventsDetails" roleURI="http://www.protalix.com/role/DisclosureSubsequentEventsDetails" />
  <arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" />
  <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" />
  <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" />
  <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" />
  <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" />
  <arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/notAll" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#notAll" />
  <definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended" xlink:title="Extensible Enumeration Domain Members" />
  <definitionLink xlink:role="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfOperations" xlink:type="extended" xlink:title="00200 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain_637647094305647835" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain_637647094305647835" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherIncome" xlink:label="us-gaap_OtherIncome" />
    <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_OtherIncome" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EarningsPerShareBasicAndDiluted" xlink:label="us-gaap_EarningsPerShareBasicAndDiluted" />
    <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_EarningsPerShareBasicAndDiluted" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" xlink:label="us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" />
    <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_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfOperationsParenthetical" xlink:type="extended" xlink:title="00205 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Parenthetical)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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_StatementTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_637647094305678080" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain_637647094305678080" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="us-gaap_CostOfSalesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_CostOfSalesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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/StatementCondensedConsolidatedStatementsOfChangesInStockholdersEquityCapitalDeficiency" xlink:type="extended" xlink:title="00300 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CHANGES IN STOCKHOLDERS' EQUITY (CAPITAL DEFICIENCY)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_637647094305678080" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain_637647094305678080" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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-20210630.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="plx-20210630.xsd#plx_AdjustmentsToAdditionalPaidInCapitalReceivablesFromSaleOfCommonStockAndWarrants" xlink:label="plx_AdjustmentsToAdditionalPaidInCapitalReceivablesFromSaleOfCommonStockAndWarrants" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_AdjustmentsToAdditionalPaidInCapitalReceivablesFromSaleOfCommonStockAndWarrants" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.xsd#plx_StockIssuedDuringPeriodValueSalesAgreement" xlink:label="plx_StockIssuedDuringPeriodValueSalesAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_StockIssuedDuringPeriodValueSalesAgreement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" xlink:label="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ShareBasedCompensationRestrictedStockAwardsNetOfForfeitures" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_StockIssuedDuringPeriodValueWarrantsExercises" xlink:label="plx_StockIssuedDuringPeriodValueWarrantsExercises" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_StockIssuedDuringPeriodValueWarrantsExercises" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureFairValueMeasurementTables" xlink:type="extended" xlink:title="30303 - Disclosure - FAIR VALUE MEASUREMENT (Tables)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain_637647094305708034" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain_637647094305708034" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_Notes2021Member" xlink:label="plx_Notes2021Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="plx_Notes2021Member" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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/DisclosureSignificantAccountingPoliciesDetails" xlink:type="extended" xlink:title="40101 - Disclosure - SIGNIFICANT ACCOUNTING POLICIES (Details)">
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_SignificantAccountingPoliciesTable" xlink:label="plx_SignificantAccountingPoliciesTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_637647094305718074" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_637647094305718074" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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-20210630.xsd#plx_ChiesiAgreementsMember" xlink:label="plx_ChiesiAgreementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiAgreementsMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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_ChiesiAgreementsMember" xlink:to="plx_ChiesiUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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_ChiesiAgreementsMember" xlink:to="plx_ChiesiExUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_SarcomedUsaInc.AgreementMember" xlink:label="plx_SarcomedUsaInc.AgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_SarcomedUsaInc.AgreementMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:label="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="dei_LegalEntityAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.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="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain_637647094305718074" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain_637647094305718074" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="plx_SignificantAccountingPoliciesTable" xlink:to="srt_StatementGeographicalAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain_637647094305728072" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain_637647094305728072" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember_637647094305728072" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember_637647094305728072" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="6" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_637647094305748798" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_637647094305748798" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermDebtTypeAxis" xlink:label="us-gaap_ShortTermDebtTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="7" xlink:from="plx_SignificantAccountingPoliciesTable" xlink:to="us-gaap_ShortTermDebtTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermDebtTypeDomain" xlink:label="us-gaap_ShortTermDebtTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ShortTermDebtTypeAxis" xlink:to="us-gaap_ShortTermDebtTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermDebtTypeDomain" xlink:label="us-gaap_ShortTermDebtTypeDomain_637647094305748798" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_ShortTermDebtTypeAxis" xlink:to="us-gaap_ShortTermDebtTypeDomain_637647094305748798" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleNotesPayableMember" xlink:label="us-gaap_ConvertibleNotesPayableMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShortTermDebtTypeDomain" xlink:to="us-gaap_ConvertibleNotesPayableMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="plx-20210630.xsd#plx_LicenseAgreementInitialCashPayment" xlink:label="plx_LicenseAgreementInitialCashPayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_LicenseAgreementInitialCashPayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_TermToSignSupplyAgreement" xlink:label="plx_TermToSignSupplyAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_TermToSignSupplyAgreement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:label="us-gaap_SharesIssuedPricePerShare" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_UpfrontNonrefundableNonCreditablePaymentReceivable" xlink:label="plx_UpfrontNonrefundableNonCreditablePaymentReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_UpfrontNonrefundableNonCreditablePaymentReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_AdditionalAmountsPayableToCoverDevelopmentCosts" xlink:label="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_AdditionalAmountsPayableToCoverDevelopmentCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" xlink:label="plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_MaximumEntitlementOfDevelopmentCostsToCoverPerYear" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_AgreementAmendmentPaymentReceivable" xlink:label="plx_AgreementAmendmentPaymentReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_AgreementAmendmentPaymentReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" xlink:label="plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_ChangeInAmountReceivableForAchievementOfRegulatoryAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" xlink:label="plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_AdditionalAmountPayableForAchievementOfRegulatoryAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_PaymentOnNetSalesPercentage" xlink:label="plx_PaymentOnNetSalesPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_PaymentOnNetSalesPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" xlink:label="plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_CollaborativeArrangementRevenuesExpensesSharingPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtCurrent" xlink:label="us-gaap_ConvertibleDebtCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_ConvertibleDebtCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_RevenuePerformanceObligationNumber" xlink:label="plx_RevenuePerformanceObligationNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="20" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="plx_RevenuePerformanceObligationNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="21" xlink:from="plx_SignificantAccountingPoliciesLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureFairValueMeasurementLiabilityComponentWasValuedBasedOnIncomeApproachDetails" xlink:type="extended" xlink:title="40301 - Disclosure - FAIR VALUE MEASUREMENT - The liability component was valued based on the Income Approach (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_637647094305898116" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_637647094305898116" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain_637647094305898116" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeDomain_637647094305898116" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="40302 - Disclosure - FAIR VALUE MEASUREMENT - Additional Information (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermBorrowings" xlink:label="us-gaap_ShortTermBorrowings" />
    <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_ShortTermBorrowings" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtFairValueDisclosures" xlink:label="us-gaap_ConvertibleDebtFairValueDisclosures" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ConvertibleDebtFairValueDisclosures" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureRevenuesCompanySDisaggregationOfRevenuesDetails" xlink:type="extended" xlink:title="40401 - Disclosure - REVENUES - Company's disaggregation of revenues (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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_StatementTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.xsd#plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" xlink:label="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiUsAgreementAndChiesiExUsAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.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="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="plx_ChiesiExUSAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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-20210630.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/2020/country-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ChangeInAccountingEstimateByTypeAxis" xlink:label="us-gaap_ChangeInAccountingEstimateByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ChangeInAccountingEstimateByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ChangeInAccountingEstimateTypeDomain" xlink:label="us-gaap_ChangeInAccountingEstimateTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ChangeInAccountingEstimateByTypeAxis" xlink:to="us-gaap_ChangeInAccountingEstimateTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ChangeInAccountingEstimateTypeDomain" xlink:label="us-gaap_ChangeInAccountingEstimateTypeDomain_637647094305938096" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_ChangeInAccountingEstimateByTypeAxis" xlink:to="us-gaap_ChangeInAccountingEstimateTypeDomain_637647094305938096" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ChangeInAccountingMethodAccountedForAsChangeInEstimateMember" xlink:label="us-gaap_ChangeInAccountingMethodAccountedForAsChangeInEstimateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ChangeInAccountingEstimateTypeDomain" xlink:to="us-gaap_ChangeInAccountingMethodAccountedForAsChangeInEstimateMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="plx-20210630.xsd#plx_ReductionToAccumulatedRevenueRecognized" xlink:label="plx_ReductionToAccumulatedRevenueRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ReductionToAccumulatedRevenueRecognized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_VariableConsideration" xlink:label="plx_VariableConsideration" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_VariableConsideration" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_ProceedsFromVariableConsideration" xlink:label="plx_ProceedsFromVariableConsideration" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="plx_ProceedsFromVariableConsideration" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureStockTransactionsDetails" xlink:type="extended" xlink:title="40501 - Disclosure - STOCK TRANSACTIONS (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_SaleOfStockMaximumOfferingPrice" xlink:label="plx_SaleOfStockMaximumOfferingPrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="plx_SaleOfStockMaximumOfferingPrice" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.protalix.com/role/DisclosureSubsequentEventsDetails" xlink:type="extended" xlink:title="40601 - Disclosure - SUBSEQUENT EVENTS (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventTable" xlink:label="us-gaap_SubsequentEventTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_637647094305968039" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain_637647094305968039" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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_SubsequentEventTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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-20210630.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-20210630.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" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermBorrowings" xlink:label="us-gaap_ShortTermBorrowings" />
    <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_ShortTermBorrowings" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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_SubsequentEventLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_DebtConversionConvertedInstrumentAmountCash" xlink:label="plx_DebtConversionConvertedInstrumentAmountCash" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_DebtConversionConvertedInstrumentAmountCash" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_DebtInstrumentConvertibleConversionShareNumber" xlink:label="plx_DebtInstrumentConvertibleConversionShareNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_DebtInstrumentConvertibleConversionShareNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_DebtInstrumentConvertibleBaseValueForConversionRate" xlink:label="plx_DebtInstrumentConvertibleBaseValueForConversionRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_DebtInstrumentConvertibleBaseValueForConversionRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="plx-20210630.xsd#plx_PercentageOfPremiumToClosingPriceOfStock" xlink:label="plx_PercentageOfPremiumToClosingPriceOfStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="plx_PercentageOfPremiumToClosingPriceOfStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTerm" xlink:label="us-gaap_DebtInstrumentTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_SubsequentEventLineItems" xlink:to="us-gaap_DebtInstrumentTerm" priority="1" use="optional" />
  </definitionLink>
</linkbase>
