Abstract: Objective To observe the influence of interleukin-6 (IL-6) on liver cancer SMMC-7721 cells' proliferation, invasion and metastasis, and explore its mechanism. Methods SMMC-7721 cells were cultured in vitro, IL-6 (0, 5, 10, 20, 40 ng/ml) ofdifferent concentrations and/or AKT inhibitor LY294002 were added. MTT, wound healing assay, Transwell invasion assay, cell adhesion assay were used todetect changes in cell proliferation, metastasis and invasion; Western blot method was used todetect the expression quantity of AKT, p-AKT, MMP-9, CD44, and Ezrin protein. Results The IL - 6 (5, 10, 20 ng/ml) promoted the cell proliferation rate, the healing rate of scratches, the number of invading cells and adherent cell absorbance value (P< 0.05) concentration-dependently; and there was no statistically significantdifference between concentration of 20 ng/ml and 40 ng/ml of IL - 6 (P> 0.05). The cell proliferation rate (62.76%±6.86%), healing rate of scratches (92.37%±9.38%), number of invading cells (174.41±15.14), adherent cell absorbance value (0.531±0.055), and the protein expression of P - AKT, MMP - 9, CD44 and Ezrin of IL - 6 optimal effect concentration group (20 ng/ml) were higher than those of control group and IL-6 (20 ng/ml) + LY296002 (20 µmol/L) group (P< 0.05). There was no statistical significance in AKT protein expression between each group (P> 0.05). Conclusion IL-6 can influence the expression of MMP-9, CD44, Ezrin protein by AKT pathway, and promote proliferation, invasion and metastasis of liver cancer cell.