Objective: To study the effect of triptolide on human hepatocelluar carcinoma HepG2 cells proliferation and apoptosis in vitro and in vivo, as well as its possible mechanisms. Methods:HepG2 cells were cultured in triptolide media with different concentrations. Cell viability was assessed by MTT assay. Cell apoptosis was observed by flow cytometry(FCM). The heat shock protein 70(HSP70) was assayed by Western blotting and RT-PCR methods. Caspase-3 activity was examined by caspase-3 colorimetric assay. In a xenograft tumor model, the control group and experimental group were treated with 0.9% NaCl solution and triptolide(0.4mg/kg,q.d.), respectively .Three weeks after treatment, the influence of triptolide on the growth of hepatocellular carcinoma was observed. Results:Triptolide treatment resulted in dose- and time-dependent proliferation and apoptosis of HepG2 cells(P < 0.05). Triptolide decreased HSP70 mRNA and protein levels in a dose-dependent pattern, whereas caspase-3 activity was significantly increased in a dose-dependent manner. Moreover, Mice receiving triptolide therapy had significantly smaller tumors than controls(P < 0.05). Conclusion:Triptolide causes human hepatocelluar carcinoma HepG2 cells death in vitro and in vivo by inducing apoptosis and its mechanism of action might be mediated via the inhibition of HSP70 and up-regulation of caspase-3 activity.