Background:　Liver　transplantation　(LT)　is　the　only　effective　therapy　for　end-stage　liver　diseases,　but　some　patients　usually　present　with　serious　infection　and　immune　rejection.　Those　with　immune　rejection　require　long-term　administration　of　immunosuppressants,　leading　to　serious　adverse　effects.　Mesenchymal　stem　cells　(MSCs)　have　various　advantages　in　immune　regulation　and　are　promising　drugs　most　likely　to　replace　immunosuppressants.　Summary:　This　study　summarized　the　application　of　MSCs　monotherapy,　its　combination　with　immunosuppressants,　MSCs　genetic　modification,　and　MSCs　derivative　therapy　(cell-free　therapy)　in　LT.　This　may　deepen　the　understanding　of　immunomodulatory　role　of　MSCs　and　promote　the　application　of　MSCs　in　immune　rejection　treatment　after　LT.　Key　Messages:　MSCs　could　attenuate　ischemia-reperfusion　injury　and　immune　rejection.　There　is　no　consensus　on　the　effects　of　types　and　concentrations　of　immunosuppressants　on　MSCs.　Although　genetically　modified　MSCs　have　contributed　to　better　outcomes　to　some　extent,　the　best　modification　is　still　unclear.　Besides,　multiple　clinical　complications　developed　frequently　after　LT.　Unfortunately,　there　are　still　few　studies　on　the　polygenic　modification　of　MSCs　for　the　simultaneous　treatment　of　these　complications.　Therefore,　more　studies　should　be　performed　to　investigate　the　potency　of　multi-gene　modified　MSCs　in　treating　complications　after　LT.　Additionally,　MSC　derivatives　mainly　include　exosomes,　extracellular　vesicles,　and　conditioned　medium.　Despite　therapeutic　effects,　these　three　therapies　still　have　some　limitations　such　as　heterogeneity　between　generations　and　that　they　cannot　be　quantified　accurately.　©　2023　S.　Karger　AG,　Basel.