The effects of exogenous expression of p21(WAF1/CIP1) in hepatoma cells were examined. Two stably p21(WAF1/CIP1)-transfected clones and one clone transfected with expression vector only were used for study. Introduction of p21(WAF1/CIP1) resulted in significant cell growth inhibition, and the magnitude of the cell growth inhibition in these transfected cells was proportional to the level of p21(WAF1/CIP1) protein expressed. Exogenous p21(WAF1/CIP1) expression also significantly enhanced chemosensitivity to cisplatin. In addition, apoptosis occurred earlier in cells transfected with p21(WAF1/CIP1) after cisplatin treatment. These findings raise the potential that forced upregulation of p21(WAF1/CIP1) in hepatocellular carcinoma (HCC) may reduce the doses of cisplatin to achieve similar responses and suggest the possible use of p21(WAF1/CIP1) in HCC treatment.