Hepatocellular carcinoma is one of the most lethal malignancies and there is no effective preventive measure in this highly malignant disease to date. In the present study, we investigated the chemopreventive potential of capsaicin (8-methyl-N- vanillyl-6-nonenamide), the principal pungent ingredient found in hot red pepper, in SK-Hep-1 hepatocellular carcinoma cells. Treatment of capsaicin inhibited growth of SK-Hep-1 cells in a concentration-dependent manner while 4-methoxy capsaicin (Met-capsaicin) was less potent. This inhibitory effect of capsaicin on SK-Hep-1 cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation and nuclear condensation. Furthermore, capsaicin prominently reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and consequently increased caspase-3 activity. These results demonstrate that capsaicin efficiently induced apoptosis in SK-Hep-1 cells through a caspase-3-dependent mechanism, which may contribute to its chemopreventive function.