Although　mesenchymal　stem　cell　(MSC)　transplantation　provides　an　alternative　strategy　for　end-stage　liver　disease　(ESLD),　further　widespread　application　of　MSC　therapy　is　limited　owing　to　low　cell　engraftment　efficiency.　Improving　cell　engraftment　efficiency　plays　a　critical　role　in　enhancing　MSC　therapy　for　liver　diseases.　In　this　review,　we　summarize　the　current　status　and　challenges　of　MSC　transplantation　for　ESLD.　We　also　outline　the　complicated　cell-homing　process　and　highlight　how　low　cell　engraftment　efficiency　is　closely　related　to　huge　differences　in　extracellular　conditions　involved　in　MSC　homing　journeys　ranging　from　constant,　controlled　conditions　in　vitro　to　variable　and　challenging　conditions　in　vivo.　Improving　cell　survival　and　homing　capabilities　enhances　MSC　engraftment　efficacy.　Therefore,　we　summarize　the　current　strategies,　including　hypoxic　priming,　drug　pretreatment,　gene　modification,　and　cytokine　pretreatment,　as　well　as　splenectomy　and　local　irradiation,　used　to　improve　MSC　survival　and　homing　capability,　and　enhance　cell　engraftment　and　therapeutic　efficiency　of　MSC　therapy.　We　hope　that　this　review　will　provide　new　insights　into　enhancing　the　efficiency　of　MSC　engraftment　in　liver　diseases.