<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  10.1.0.3 -->
<!--Based on XBRL 2.1-->
<!--Created on: 11/13/2022 9:07:37 PM-->
<!--Modified on: 11/13/2022 9:07:37 PM-->
<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" 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-20220930.xsd#StatementCondensedConsolidatedBalanceSheets" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedBalanceSheets" />
  <roleRef xlink:type="simple" xlink:href="plx-20220930.xsd#StatementCondensedConsolidatedStatementsOfOperations" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfOperations" />
  <roleRef xlink:type="simple" xlink:href="plx-20220930.xsd#StatementCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" />
  <roleRef xlink:type="simple" xlink:href="plx-20220930.xsd#DisclosureInventoriesScheduleOfInventoryDetails" roleURI="http://www.protalix.com/role/DisclosureInventoriesScheduleOfInventoryDetails" />
  <calculationLink xlink:role="http://www.protalix.com/role/StatementCondensedConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_638039704559619800" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_638039704559619800" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638039704559619800" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_638039704559629815" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_ShortTermBankDeposits" xlink:label="plx_ShortTermBankDeposits_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638039704559619800" xlink:to="plx_ShortTermBankDeposits_638039704559629815" order="2" use="optional" weight="1" priority="2" />
    <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_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638039704559619800" xlink:to="us-gaap_AccountsReceivableNetCurrent_638039704559629815" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="us-gaap_OtherAssetsCurrent_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638039704559619800" xlink:to="us-gaap_OtherAssetsCurrent_638039704559629815" order="4" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638039704559619800" xlink:to="us-gaap_InventoryNet_638039704559629815" order="5" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent" xlink:label="us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent_638039704559629815" order="2" use="optional" weight="1" priority="4" />
    <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_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_638039704559629815" order="3" use="optional" weight="1" priority="4" />
    <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_638039704559629815" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_638039704559629815" order="4" use="optional" weight="1" priority="6" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_637041422967477240" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_637041422967477240" xlink:to="us-gaap_Liabilities_638039704559639839" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesNoncurrent" xlink:label="us-gaap_LiabilitiesNoncurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_638039704559639839" xlink:to="us-gaap_LiabilitiesNoncurrent_638039704559639839" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="us-gaap_ConvertibleDebtNoncurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638039704559639839" xlink:to="us-gaap_ConvertibleDebtNoncurrent_638039704559639839" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638039704559639839" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_638039704559639839" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PensionAndOtherPostretirementAndPostemploymentBenefitPlansLiabilitiesNoncurrent" xlink:label="us-gaap_PensionAndOtherPostretirementAndPostemploymentBenefitPlansLiabilitiesNoncurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638039704559639839" xlink:to="us-gaap_PensionAndOtherPostretirementAndPostemploymentBenefitPlansLiabilitiesNoncurrent_638039704559639839" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638039704559639839" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_638039704559639839" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_638039704559639839" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_638039704559639839" xlink:to="us-gaap_LiabilitiesCurrent_638039704559639839" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableTradeCurrent" xlink:label="us-gaap_AccountsPayableTradeCurrent_638039704559649844" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638039704559639839" xlink:to="us-gaap_AccountsPayableTradeCurrent_638039704559649844" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableOtherCurrent" xlink:label="us-gaap_AccountsPayableOtherCurrent_638039704559649844" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638039704559639839" xlink:to="us-gaap_AccountsPayableOtherCurrent_638039704559649844" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_638039704559649844" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638039704559639839" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_638039704559649844" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_638039704559649844" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638039704559639839" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_638039704559649844" order="4" use="optional" weight="1" />
    <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_638039704559649844" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_637041422967477240" xlink:to="us-gaap_StockholdersEquity_638039704559649844" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink 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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="loc_us-gaap_NetIncomeLoss" />
    <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_638039704559659860" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_638039704559659860" order="1" use="optional" weight="1" />
    <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_638039704559659860" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638039704559659860" xlink:to="us-gaap_CostOfRevenue_638039704559659860" order="1" use="optional" weight="-1" priority="2" />
    <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_638039704559659860" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638039704559659860" xlink:to="us-gaap_ResearchAndDevelopmentExpense_638039704559659860" order="2" use="optional" weight="-1" priority="2" />
    <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_638039704559659860" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638039704559659860" xlink:to="us-gaap_Revenues_638039704559659860" order="3" use="optional" weight="1" priority="2" />
    <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_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638039704559659860" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_638039704559669816" order="4" use="optional" weight="-1" priority="2" />
    <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_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss" xlink:to="us-gaap_NonoperatingIncomeExpense_638039704559669816" order="2" use="optional" weight="1" />
    <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_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_638039704559669816" xlink:to="us-gaap_OtherNonoperatingExpense_638039704559669816" order="1" use="optional" weight="-1" />
    <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_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_638039704559669816" xlink:to="us-gaap_OtherNonoperatingIncome_638039704559669816" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherIncome" xlink:label="us-gaap_OtherIncome_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss" xlink:to="us-gaap_OtherIncome_638039704559669816" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.protalix.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00400 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_637168086008773890" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_637168086008773890" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" order="1" use="optional" weight="1" priority="7" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_638039704559669816" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_ShareBasedCompensation_638039704559669816" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation" xlink:label="us-gaap_Depreciation_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_Depreciation_638039704559679811" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForeignCurrencyTransactionGainLossUnrealized" xlink:label="us-gaap_ForeignCurrencyTransactionGainLossUnrealized_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_ForeignCurrencyTransactionGainLossUnrealized_638039704559679811" order="3" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PensionAndOtherPostretirementBenefitExpense" xlink:label="us-gaap_PensionAndOtherPostretirementBenefitExpense_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_PensionAndOtherPostretirementBenefitExpense_638039704559679811" order="4" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_GainLossOnAmountsFundedInRespectOfEmployeeRightsUponRetirement" xlink:label="plx_GainLossOnAmountsFundedInRespectOfEmployeeRightsUponRetirement_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="plx_GainLossOnAmountsFundedInRespectOfEmployeeRightsUponRetirement_638039704559679811" order="5" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSaleOfPropertyPlantEquipment" xlink:label="us-gaap_GainLossOnSaleOfPropertyPlantEquipment_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_GainLossOnSaleOfPropertyPlantEquipment_638039704559679811" order="6" use="optional" weight="-1" priority="3" />
    <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_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt_638039704559679811" order="7" use="optional" weight="-1" />
    <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_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_AmortizationOfFinancingCostsAndDiscounts_638039704559679811" order="8" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_638039704559679811" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_638039704559679811" order="9" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable_638039704559689804" order="10" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_ChangeInOperatingLeaseRightOfUseAssets" xlink:label="plx_ChangeInOperatingLeaseRightOfUseAssets_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="plx_ChangeInOperatingLeaseRightOfUseAssets_638039704559689804" order="11" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_IncreaseDecreaseInInventories_638039704559689804" order="12" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_638039704559689804" order="13" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_ProfitLoss_638039704559689804" order="14" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities" xlink:label="us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638039704559669816" xlink:to="us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_638039704559689804" order="15" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_637168086008773890" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" order="2" use="optional" weight="1" priority="7" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_IncreaseDecreaseInBankDeposits" xlink:label="plx_IncreaseDecreaseInBankDeposits_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="plx_IncreaseDecreaseInBankDeposits_638039704559699798" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_ProceedsFromSaleOfShortTermDeposits" xlink:label="plx_ProceedsFromSaleOfShortTermDeposits_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="plx_ProceedsFromSaleOfShortTermDeposits_638039704559699798" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_638039704559699798" order="3" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:label="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_638039704559699798" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForProceedsFromOtherInvestingActivities" xlink:label="us-gaap_PaymentsForProceedsFromOtherInvestingActivities_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="us-gaap_PaymentsForProceedsFromOtherInvestingActivities_638039704559699798" order="5" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_IncreaseDecreaseInRestrictedDeposit" xlink:label="plx_IncreaseDecreaseInRestrictedDeposit_638039704559699798" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638039704559689804" xlink:to="plx_IncreaseDecreaseInRestrictedDeposit_638039704559699798" order="6" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_637168086008773890" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" order="3" use="optional" weight="1" priority="8" />
    <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_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" xlink:to="us-gaap_RepaymentsOfNotesPayable_638039704559709789" order="1" use="optional" weight="-1" priority="2" />
    <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_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" xlink:to="us-gaap_RepaymentsOfConvertibleDebt_638039704559709789" order="2" use="optional" weight="-1" />
    <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_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock_638039704559709789" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="plx-20220930.xsd#plx_ProceedsFromIssuanceOfCommonStockAndWarrantsNetOfIssuanceCost" xlink:label="plx_ProceedsFromIssuanceOfCommonStockAndWarrantsNetOfIssuanceCost_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" xlink:to="plx_ProceedsFromIssuanceOfCommonStockAndWarrantsNetOfIssuanceCost_638039704559709789" order="4" use="optional" weight="1" priority="2" />
    <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_638039704559709789" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638039704559709789" xlink:to="us-gaap_ProceedsFromWarrantExercises_638039704559709789" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents" xlink:label="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_638039704559719797" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_637168086008773890" xlink:to="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_638039704559719797" order="4" use="optional" weight="1" priority="7" />
  </calculationLink>
  <calculationLink xlink:role="http://www.protalix.com/role/DisclosureInventoriesScheduleOfInventoryDetails" xlink:type="extended" xlink:title="40201 - Disclosure - INVENTORIES (Schedule of Inventory) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="loc_us-gaap_InventoryNet" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterialsNetOfReserves" xlink:label="us-gaap_InventoryRawMaterialsNetOfReserves_638039704559719797" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet" xlink:to="us-gaap_InventoryRawMaterialsNetOfReserves_638039704559719797" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcessNetOfReserves" xlink:label="us-gaap_InventoryWorkInProcessNetOfReserves_638039704559719797" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet" xlink:to="us-gaap_InventoryWorkInProcessNetOfReserves_638039704559719797" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoodsNetOfReserves" xlink:label="us-gaap_InventoryFinishedGoodsNetOfReserves_638039704559719797" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet" xlink:to="us-gaap_InventoryFinishedGoodsNetOfReserves_638039704559719797" order="3" use="optional" weight="1" />
  </calculationLink>
</link:linkbase>
