Recent studies have provided strong evidence that many daily-consumed dietary compounds possess cancer-protective properties that might interrupt the carcinogenesis process. Berberine is a main component of coptis. We further demonstrated that berberine (50 μM) exhibited significant cytotoxicity in humen hepatocellular carcinoma HepG2 cells but is ineffective in Chang liver cells. After berberine-treatment to HepG2 cells, mitochondrial membrane potential (△ψm) were lost at 24 h and activation of Fas at 12 h were also. These result provided that potential of anti-hepatoma activity of berberine may be mediated through an inhibition of mitochondria pathway.