Objective:To test the role of psoralidin in human liver cancer HepG2 cells in vitro.Methods:Cell viability was assessed by methylthiazolyldiphenyl-tetrazolum bromide assay and apoptotic cells were labeled by annexin V then sorted by flow cytometry.Protein expressions of caspase-3,caspase-8,caspase-9,Bax,Bid,Bcl-2,Bcl-xL and p53 were examined by westem blot while activity of caspase-3,-8 and-9 were also determined.Results:Psoralidin reduces cell viability greatly in a time dependent manner (64％,40％,21％,12％ at 2,6,24 and 48 h treatment with 64 μ mol/L psoralidin respectively) and up-regulates activities of caspase-3,-8 and-9 in a concentration dependent manner (between 4 to 64 μ mol/L).Psoralidin also increases the expression of pro-apoptosis genes Bax,Bid and p53 while decreases the expression of pro-survival genes Bcl-2 and Bcl-xL,both in a concentration dependent manner between 4 and 64 μ mol/L (P＜0.05 at 16 and 64 p mol/L).Caspase-3 inhibitor (Ac-DEVD-CHO at concentrations between 10 to 20 μ mol/L),p53 inhibitor (pifithrin-α at 5 μ mol/L)and cyclosporin A can attenuate the apoptotic effect of psoralidin.Conclusion:The cytotoxic role of psoralidin might work through both intrinsic and extrinsic apoptotic pathway.