Background: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been considered as a promising cell source in liver diseases. miRNAs have been shown to play an important role in hepatic differentiation of hUC-MSCs. The study seeks to explore whether miR122 and miR185 could affect induction of hUC-MSCs into hepatic differentiation. Methods: miR122 and miR185 stable overexpression by hUC-MSCs were firstly created, then hUC-MSCs were cultured by hepatic differentiation conditional medium. After 28 days culture in hepatic inducing conditional medium, hepatic markers expressed by these cells were detected by qRT-PCR and western-blot. The cell functions were also evaluated by PAS staining and ICG phagocytosis. Results: Our results demonstrated that at the end of 28 days, hUC-MSCs overexpressing miR122 had increasing expression of hepatocyte markers including AFP, ALB, CK18, CK19 and HNF4α in both mRNA level and protein ecpression, while in the miR185 overexpression group, hUC-MSCs showed decreasing expression of hepatocyte markers. Moreover, there was also improvement of glycogen deposits as well as ICG phagocytosis ability in the hepatic inducing miR122 overexpression cells, while in the hepatic inducing miR185 overexpression group, hUC-MSCs showed decreasing glycogen deposits and ICG phagocytosis ability. Conclusions: We thus speculate that it is possible to promote hepatic differentiation of hUC-MSCs by overexpression of miR122 and this effect may be inhibited by miR185 overexpression. It seems miR122 and miR185 have an antagonistic effect on hUC-MSCs hepatic differentiation. Overexpression of certain kind of miRNA in cells by transfection or other gene modification skills could be an effective way to modulate stem cell fate.