Development of new treatments and identification of novel therapeutic drug targets are urgently needed for hepatocellular carcinoma (HCC).EZH2 is a member of polycomb gene (PcG) family with critic roles in cellular differentiation and embryonic development.Recently, EZH2 has been reported to, implicate in the progression and metastasis of several cancers.EZH2 was overexpressed in both HCC biopsy samples and HCC cell lines as compared with pared normal liver tissue and nontumorigenic hepatocytes.We firstly developed a lentiviral vector containing short hairpin RNA (shRNA) targeting EZH2 and knocked down EZH2 expression in HCC cells.Cell growth in vitro and tumor formation in vivo were significantly inhibited with EZH2 knock-down, suggesting the critic role of EZH2 in tumorigenecity.