Irigenin has been reported to exhibit remarkable anticancer effects against several human cancers. Nonetheless, the anticancer effects of irigenin against the human liver cancer cells are still largely unexplored. Consistently, this study was designed to evaluate the anticancer effects of irigenin against human liver cancer cells and to unveil the underlying molecular mechanisms. The results showed that irigenin significantly (p<0.05) inhibited the growth of the human HepG2 and SNU-182 liver cancer cells with an IC50 value of 14 <mu>M. Nonetheless, the cytotoxic effects of irigenin against the normal THLE-2 cells were comparatively lower as evident from the IC50 of 120 mu M. The AO/EB and DAPI staining showed that irigenin induces apoptosis in the human liver cancer cells. Annexin V/PI staining assay revealed a significant (p<0.05) increase in the percentage of apoptotic HepG2 and SNU-182 liver cancer cells upon treatment with irigenin. It was found that the number of apoptotic HepG2 and SNU-182 cells enhanced from 2.3 to 41.75% and 1.16 to 51.9% at IC50, respectively. Western blot showed a considerable increase in Bax and decrease in the Bcl-2 expression upon irigenin treatment further confirming the induction of apoptosis. Flow cytometric analysis revealed that irigenin also induces G2/M cell cycle arrest of HepG2 and SNU-182 cells. The percentage of G2/M phase HepG2 and SNU-182 cells increased from 17.92 to 34.35% and 23.97 to 38.23% at IC50, respectively This was also accompanied by decrease in the expression of CDK1 and Cyclin-B in HepG2 and SNU-182 cells. Taken together, the results of the present study suggest that irigenin inhibits the growth of the human liver cancer cells via induction of apoptosis and cell cycle arrest. These results point towards the potential of irigenin as a lead for the development of chemotherapy for liver cancer.