[Objectives] To observe the effects of oxymatrine on the proliferation, invasion and migration of hepatocellular carcinoma cells, and to explore its possible molecular mechanism. [Methods]The hepatocellular carcinoma cell line Hep G2 was randomly divided into the negative control group and the low, medium and high concentration groups of oxymatrine. The negative control group was added to the cell culture medium, and the low, medium and high concentration groups of oxymatrine were added to the oxymatrine and cell culture medium with the final concentration of 1. 0, 2. 0 and 4. 0 mg/m L. The proliferation of each group was measured by MTT assay, and the inhibition rate of cell proliferation was calculated. The invasion and migration ability of each group was determined using Transwell chamber assay. The expression of E-cadherin and CD44 mRNA in each group was detected using Real-time PCR, while the expression of E-cadherin and CD44 protein was detected using Western blotting method. [Results] The inhibition rate of cell proliferation in the high concentration group of oxymatrine was higher than that in the medium and low concentration groups, and the inhibition rate of cell proliferation of medium concentration group was higher than that in the low concentration group. In the cell invasion and cell migration experiments, the number of transmembrane cells of low, medium and high concentration groups of oxymatrine was less than that in the negative control group(P < 0.05), the number of transmembrane cells of high concentration groups of oxymatrine was less than that in medium and low concentration groups, and the number of transmembrane cells of medium concentration group was less than in that of the low concentration group(P < 0.05). Compared with the negative control group, the expression of E-cadherin mRNA and protein increased in the low, medium and high concentration groups of oxymatrine, while the expression of CD44 mRNA and protein decreased(P < 0.05). [Conclusions] Oxymatrine has the effect of inhibiting the proliferation, invasion and migration of hepatocellular carcinoma cell line Hep G2 in vitro. The higher the concentration, the more significant the effect will be. The mechanism is possibly connected with the up-regulation of E-cadherin expression and down-regulation of CD44 expression. [ABSTRACT FROM AUTHOR]