Objective: To investigate the antitumor effect of ginsenoside Rg3 combined with cisplatin on hepatocarcinoma mice. Methods: Mouse solid tumor model and ascites tumor model were constructed by H22 hepatocellular carcinoma cells. All groups were divided into a control group, a cisplatin group, a ginsenoside Rg3 group and a combination group. The inhibitory effect of drugs on hepatocellular carcinoma were evaluated by weighing mice. The survival time of mice was calculated to detect the effect of drugs on survival. The effect of the drug on the immune system of mice was detected by detecting the thymus (spleen) gland index and white blood cells counts. Effects of drugs on the structure of hepatocellular carcinoma cells in mice were detected by HE staining. Results: Compared with the control group, the ginsenoside Rg3 group, the combination group and the cisplatin group had significant inhibitory effect on tumor growth in mice. The inhibitory rates were 45.83%, 27.50%, and 51.66%. Combination therapy significantly inhibited tumor growth. Ginsenoside Rg3 combined with cisplatin in mice prolonged the life of 66.83%. Ginsenoside Rg3 promoted the growth of mice, against drug toxicity of cisplatin. Ginsenoside Rg3 attenuated cisplatin-induced leukopenia, spleen and thymic atrophy and other drug toxicity. In the combined treatment group, hepatocellular carcinoma cells had obvious chromatin agglutination. Conclusion: Ginsenoside Rg3 can significantly inhibit the growth of tumor in mice, combination with drug cisplatin can enhance the effect of chemotherapy, to a certain extent, inhibition of cisplatin toxicity.