OBJECTIVE: Keratinocyte growth factor (KGF) has a demonstrated role in the prevention of cirrhosis during liver regeneration. Previous studies have shown that transplantation of human umbilical cord mesenchymal stem cells (HUCMSCs) reduces the development of cirrhosis after liver injury. However, whether KGF may be involved in the underlying molecular mechanisms remains unknown. Here we addressed this question. MATERIALS AND METHODS: We did HUCMSC transplantation in mice that had developed cirrhosis by carbon tetrachloride (CCl4). The effects of UCMSC transplantation on KGF levels and liver damage were examined. The level of a KGF-targeting microRNA, miR-199, was examined. The regulation of KGF by miR-199 was studied by bioinformatics analyses and luciferase reporter assay. RESULTS: HUCMSC transplantation significantly ameliorated the severity of liver fibrosis, reduced portal hypertension and sodium retention that were induced by CCl4. HUCMSC transplantation significantly increased the levels of KGF in the injured liver, seemingly through suppression of miR-199, which targeted 3'-UTR of KGF mRNA to inhibit its protein translation. CONCLUSIONS: HUCMSCs may ameliorate cirrhosis through activation of KGF by suppressing miR-199.