OBJECTIVE：To study the effects of paeonol combined with cisplatin on the proliferation and apoptosis of human osteosarcoma cell MG- 63 and its possible mechanism. METHODS ：MG-63 cells in logarithmic growth phase were divided into blank control group ，cisplatin group （4 µmol/L），paeonol group （50 mg/L），and low ，medium，high concentration combined groups （50，100，200 mg/L paeonol+ 4 µmol/L cisplatin ）. CCK- 8 method was used to detect the cell proliferation rate at 24，48，and 72 hours of treatment. Annexin Ⅴ-FITC/PI double staining method was used to detect the cell apoptosis rate at 24 hours of treatment. The relative expression of PI 3KCA，Akt，mTOR，P-gp and PTEN mRNA in cells were detected by qRT-PCR. RESULTS ：Compared with blank control group ，the cell proliferation rate at each time point ，and the relative expression of PI 3KCA，Akt and mTOR mRNA in cells were significantly reduced and the apoptosis rate and the relative expression of P-gp and PTEN mRNA in the cells were increased significantly （P＜0.05 or P＜0.01）. Compared with cisplatin group and paeonol group ，cell proliferation rate at each time point and the relative expression of PI 3KCA，Akt and mTOR mRNA in cells were decreased significantly in the high concentration combination group ，while the relative expression of P-gp and PTEN mRNA in the cells were significantly increased （P＜0.01）；there were statistical significance in some of the above indicators in the medium and low concentration combination groups（P＜0.05 or P＜0.01）. CONCLUSIONS ：The combination of paeonol and cisplatin could inhibit the proliferation of MG- 63 cells and promote their apoptosis ，which may be related to the down-regulation of PI 3KCA，Akt and mTOR mRNA expression ，and the up-regulation of P-gp and PTEN mRNA expression.