AIM:To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS:Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation wasdetected.RESULTS:The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid.Flow cytometric assay demonstrated that S phase cells decreased and G(0)/G(1) phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased. CONCLUSION:Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.