Abstract: Objective To observe the effects of oxaliplatin in combination with ginsenoside Rg3 on human hepatomacellular carcinoma cell line SMMC-7721 in vitro，and explore the underlying mechanism. Methods SMMC-7721 cells were treated with oxaliplatin or ginsenoside Rg3 alone or in three different schedules： oxaliplatin was given prior to， after， or simultaneously with ginsenoside Rg3.The proliferation of SMMC-7721 cells was determined by MTT assay.The cell cycle distribution and apoptosis rate were analyzed by flow cytometry. The expression of cell cycle related protein：cyclin D1 was measured by Western blotting. Results The inhibition of cell proliferation was significant when SMMC-7721 cells were treated with oxaliplatin or ginsenoside Rg3 alone or in three different schedules： oxaliplatin was given prior to，after，or simultaneously with ginsenoside Rg3.Oxaliplatin plus ginsenoside Rg3 revealed a better effect than ginsenoside Rg3 given prior to oxaliplatin（P＜0.05），similar to oxaliplatin given prior to ginsenoside Rg3（P＞0.05）. The effect of first using oxaliplatin was better than first using ginsenoside Rg3（P＜0.05）.By flow cytometry，oxaliplatin caused cell cycle arrest at S phase，G₂／M phase，while ginsenoside Rg3 blocked cells at G₀／G₁ phase.The apoptosis rate of combining oxaliplatin with ginsenoside Rg3 was similar to oxaliplatin given prior to ginsenoside Rg3（P＞0.05），they blocked cells at G₂／M phase，and both of the groups had a higher apoptotic rate than oxaliplatin given after ginsenoside Rg3（P＜0.05）.The result of Western blotting revealed that the protein level of cyclin D1 was lower in the dual-therapy groups than that in the monotherapy groups.The protein level of cyclin D1 was lower in SMMC-7721 cells treated with oxaliplatin given prior to ginsenoside Rg3 and oxaliplatin plus ginsenoside Rg3. Conclusion The dualtherapy groups have a significant inhibitory effect on the proliferation of SMMC-7721 compared to the monotherapy groups.A synergistic effect in SMMC-7721 cells receiving oxaliplatin followed by ginsenoside Rg3 is similar to that in those receiving oxaliplatin plus ginsenoside Rg3，and the efficacy of the two groups is better than that of oxaliplatin given after ginsenoside Rg3.This is probably due to that the two groups block cells at S phase and G₂／M phase，then induce apoptosis of the cells， and reduce the expression of cyclin D1.