Objective:To investigate the effects of hepatitis B virus X (HBx) on hepatocellular carcinoma (HCC) proliferation, invasion, and sorafenib resistance.Methods:HepG2 cell line infected with HBx ORF lentivirus was set as the HBx high expression group and infected with empty vector was set as the negative control group. The interference group was infected with the HBx siRNA virus based on the HBx high expression group to reduce HBx expression. Interference control group as interference group but with infected empty vector virus. Western blotting was used to measure the protein level of HBx. Cell proliferation, invasion ability, and sorafenib semi-inhibitory concentration (IC50) of HCC cells under different HBx expression levels were respectively detected by cell proliferation assay kit, Transwell invasion assay, and cell titer-glo kit.Results:Western blotting showed that the stable cell lines were successfully established. Cell proliferation of the HBx high expression group was better than that of the blank control and negative control groups, and the cell proliferation of the interference group was lower than that of the interference control and HBx high expression groups, and the differences were all statistically significant ( P<0.05). The number of cells crossing Matrigel gel was (46.2±4.1), (50.7±5.1) and (48.2±5.2) in the blank control group, negative control group, and interference group, respectively. The number of cells crossing Matrigel gel in the HBx high expression group (124.2±8.3) and the interference control group (117.2±7.5) were higher than the above three groups, respectively, and the differences were all statistically significant ( P<0.05). The IC50 of cells in the HBx high expression group and the interference control group were (5.36±0.31) μmol/L and (5.48±0.20) μmol/L, respectively, which were higher than those in the blank control group, the negative control group, and the interference group (4.75±0.22) μmol/L, (4.60±0.14) μmol/L and (3.98±0.03) μmol/L. The differences were all statistically significant ( P<0.05). Conclusion:HBx promoted the tumor proliferation and invasion of HepG2 HCC cells, enhanced the ability to sorafenib resistance, and inhibited apoptosis.