In the present work, the effect of interferon-alfa-2a on human hepatoma HepG2 cells has been studied. HepG2 cells were cultured with different concentrations of IFN-alpha of for 7 days, and then apoptotic and proliferative indexes were evaluated. It has been shown that upon such incubation, hepatoma cells were arrested in G(0)/G(1) phase; proliferative indexes were found to be decreased significantly and apoptosis rate was increased at IFN-alpha concentrations of 50 U/ml and NO U/ml compared to the control (29% +/- 4.5% and 27% +/- 4.6% vs 44% +/- 3.2%, p < 0.01; and 34% &PLUSMN; 9.6% and 43% &PLUSMN; 22% vs 0.8% &PLUSMN; 3%, p < 0.01 respectively). Colony counts per well decreased significantly at IFN-alpha concentrations of 100 U/ml compared to control. Clinical. relevance of these finding remain to be,established with further studies.