This study has demonstrated that baicalein has anticancer effectiveness against human hepatoma cells. The dose response of baicalein in Hep G2 and Hep J2 cells indicates that baicalein decreased viability >90%. In comparison, baicalein had only minimal effects on the viability of control Chang liver cells. Flow cytometric analysis showed that baicalein inhibited the cell cycle of Hep G2 cells in the S phase. In addition, baicalein treatment resulted in a decreased mitochondrial transmembrane potential and damaged the integrity of the cell membrane. The TdT-mediated dUTP-biotin nick end labeling assay results indicated that baicalein elicited a significant increase of DNA fragmentation in Hep G2 cells after incubation for 48 hours. These results indicate that baicalein is an effective antihepatoma agent with minimal influence on noncancer cells. The effects of baicalein on Hep G2 cells include inhibition of the S phase of the cell cycle, dysfunction of mitochondria, and initiation of apoptosis.