Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin on the metastasis and microangiogenesis of hepatocellular carcinoma in mice and its possible mechanism. Methods Sixty Kunming mice were used to establish H22 hepatocellular carcinoma model and were randomly divided into six groups according to the different treatment method : model group, cisplatin group, low dose Rg3 group, high dose Rg3 group, low dose Rg3 combination group and high dose Rg3 combination group. The microvascular density (MVD), and the expression of matrix metalloproteinase-2 ( MMP2), matrix metalloproteinase-9 ( MMP9) and vascular endothelial growth factor (VEGF) in each group was detected. Results 1) The body weight of the high dose Rg3 combination group and cisplatin group was increased by the smallest amount, while that of the Rg3 low dose group and high dose group increased most significantly ( P <0. 05). (2) Compared with the model group, the serum levels of CD3⁺ and CD4⁺ cells in each treatment group were increased significantly, while the levels of CD8⁺ cells were decreased significantly ( P <0. 05). The levels of CD3⁺ and CD4⁺ cells were the highest in the high dose Rg3 group, followed by the low dose Rg3 group, and the CD3⁺ and CD4⁺ cells in the low/ high dose Rg3 group was lower than that in the low dose Rg3 group ( P <0. 05). (3) Compared with the model group, the expressions of MMP2, MMP9 and VEGF in the tumor tissues of mice in each treatment group were decreased significantly ( P <0. 05). Among them, the expressions of related proteins in the high dose Rg3 combination group were significantly reduced ( P <0. 05). (4) The MVD of model group, platinum group, Rg3 low dose group, Rg3 high dose group, low dose combined group and high dose combined group were (12. 64±1. 96), (7. 73±1. 65), (9. 92±1. 45), (7. 13±1. 64), (8. 16±1. 44), and (6. 28±1. 49), respectively. There were significant differences in MVD among the six groups ( P <0. 05). Conclusions Ginsenoside Rg3 inhibits the invasion and metastasis of H22 hepatocellular carcinoma cells and has a certain coordination with cisplatin.