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Objective: To investigate the effects of EZH2 gene on the growth and migration of hepatocellular carcinoma HepG2 cell in vitro and in vivo. Methods: EZH2 shRNA plasmid vectors were constructed and transfected into HepG2 cells. A model of EZH2 gene-silencing HepG2 cell lines was constructed, and the experimental cells were classified into 3 groups: HepG2 blank control group, HepG2-V vector control group and HepG2-EZH2 (-) group. The mRNA and protein expressions of EZH2 in these three cells were detected by real-time fluorogenic quantitative PCR and Weste blotting, respectively. Cell proliferation was analyzed by MTT assay. Cells were inoculated subcutaneously in nude mice, and the growth of tumor cells in vivo was observed. Transwell chamber assay was performed to observe any change in the migration ability of cells. Results: The mRNA expression of HepG2 and HepG2-V was 100％ and (95.27±10.87)％, respectively. Compared with the control group, the mRNA level of HepG2-EZH2 (-) were significantly decreased to (20.55±13.21)％ (P<0.001). Similarly, the EZH2 protein expression were inhibited in HepG2-EZH2 (-) cells. The inhibition rate of tumor growth was 36.3％ in vitro and 52.5％ in vivo. The migration rate of the HepG2-EZH2 (-) group [(7.15±1.13)％] was significantly lower than those in the HepG2 group [(14.57±4.32)％] and the HepG2-V group [(15.21±5.22)％], with significant differences (both P<0.05). Conclusions: EZH2 silencing can effectively inhibit the proliferation and growth of HepG2 cells in vitro and in vivo and inhibit cell migration. Therefore, the EZH2 gene may be a novel target for the treatment of liver cancer.