Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation,and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticanceractivity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussureainvolucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells weretested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycledistribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR andWestern blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIEonly exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showedtypical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on humanhepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis,cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.