Tanshinone IIA (Tan IIA), isolated from the Chinese medicinal herb Danshen, has been reported to have anticancer effects in several tumor models, while its effects on renal cell carcinoma have not been studied. In the present study, we evaluated the effects of Tan IIA on growth inhibition and apoptosis in the renal cancer cell line 786-O and its mechanism of action. Results of the MTT assay indicated that the treatment of 786-O cells with Tan IIA resulted in a concentration-dependent decrease in cell viability. Flow cytometry analysis revealed that Tan IIA treatment caused apoptosis following cell cycle perturbation. Furthermore, we examined the expression of cell cycle and apoptosis-related proteins using immunoblotting, which indicated an upregulation of p53, p21, bax and caspase-3 in Tan IIA-treated cells compared with Tan IIA-untreated cells. These results suggest that the activation of p53 and the upregulation of its target genes, including p21 and bax, may be involved in the mitochondrial apoptosis induced by Tan IIA in 786-O cells.