OBJECTIVE： To investigate the effects of curcumin on proliferation and invasion of osteosarcoma cells and its mechanism. METHODS： In in vitro cell assay， osteosarcoma cells were divided into control group（dimethyl sulfoxide）， curcumin low-concentration， medium-concentration and high-concentration groups （10， 20， 40 μmol/L） and curcumin high-concentration+endogenous miR-21 simulacrum （agomiR-21） group， curcumin high-concentration+agomiR-21 negative control （NC） group. The proliferation （OD value） and invasion ability （transmembrane cells number） of human osteosarcoma cells U-2OS and MG-63 were detected by CCK-8 and Transwell chamber method； the expression of miR-21 and its target gene PDCD4 protein were detected by real-time fluorescence quantitative PCR and Western blot assay. In in vivo cell assay， MG-63 cells were inoculated in mice， and the mice were divided into blank control group （normal saline）， curcumin group （20 mg/kg）， curcumin+agomiR-21 NC group （20  mg/kg curcumin solution+50 mg/kg agomiR-21 NC solution）， curcumin+agomiR-21 group （20 mg/kg curcumin solution+50 mg/kg agomiR-21 solution） with 8 mice in each group； they were given intratumoral injection of relevant medicine once a day， for consecutive 7 d. The volume changes of the tumor were measured within 20 d after medication， and the expression of miR-21 and PDCD4 protein in tumor tissue were detected on 20th day. RESULTS： Compared with control group， the OD value and transmembrane cells number of U-2OS and MG-63 cells were decreased significantly in curcumin low-concentration， medium-concentration and high-concentration groups （P＜0.05 or P＜0.01）；the expression of miR-21 was weakened significantly in curcumin medium-concentration and high-concentration groups of U-2OS and MG-63 cells （P＜0.05 or P＜0.01）， while the expression of PDCD4 protein was strengthened significantly （P＜0.01）. Compared with curcumin high-concentration+agomiR-21 NC group， the OD value and transmembrane cells number of U-2OS and MG-63 cells were strengthened significantly in curcumin high-concentration+agomiR-21 group （P＜0.01）. Compared with blank control group， the tumor volume of mice were decreased significantly in curcumin group and curcumin+agomiR-21 NC group （P＜0.05 or P＜0.01）. The expression of miR-21 was decreased significantly in tumor tissue （P＜0.01）， while the protein expression of PDCD4 was strengthened significantly （P＜0.01）. Compared with curcumin+agomiR-21 NC group， the tumor volume of mice were increased significantly in curcumin+agomiR-21 group （P＜0.05 or P＜0.01）. The expression of miR-21 in tumor tissue were strengthened significantly （P＜0.01）， while the expression of PDCD4 protein were weakened significantly （P＜0.01）. CONCLUSIONS： Curcumin can inhibit the proliferation and invasion of human osteosarcoma cells U-2OS and MG-63， the mechanism of which may be associated with down-regulating the expression of miR-21.