The present study was designed to determine how the phytochemical genistein activates caspase-3 to cause cell cycle arrest and apoptosis. When human ovarian cancer SK-OV-3 cells were treated with $200;{mu}M$ genistein for 24 hr, cell growth decreased significantly (p<0.05). Conversely, genistein treatment significantly increased cytotoxicity (measured as lactate dehydrogenase release) under the same conditions (p<0.05). To elucidate the mechanism behind the induction of apoptosis by genistein, we studied the cell cycle and caspase-3 activation. When cells were treated with genistein, the population of cells in sub-G1 phase increased by 44.2% compared to untreated cells. Genistein caused decrease in precursor caspase-3, increase in cleaved caspase-3 and a significant increase in caspase-3 activity (p<0.05). Therefore, genistein may induce apoptosis via caspase-3 activation. However, high-dose genistein treatment must be viewed with caution because of its potential cytotoxicity.