Objective: To investigate the expression of miR-302c in HCC endothelial cells, and to explore the role of endothelial cell-specific miR-302c and its mechanism in regulating tumor growth in HCC.Methods: We investigated the regulatory role of microRNAs in endothelial cells of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-302c as the most highly down-regulated microRNA.We utilized shRNA-mediated overexpression ofmiR-302c in human umbilical vein endothelial cells (HUVECs) to investigate its impact on cell motility and the expression of several key molecular markers.Then we explored the role of endothelial cell-specific miR-302c in the regulation of tumor growth in HCC through a series of in vitro and in vivo experiments.In addition, we used reporter assays to investigate the target gene of interest ofmiR-302c.