Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose‑ and time‑dependent manner. Furthermore, in HepG2 and Huh‑7 cells, angelicin‑induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase/RAC‑α serine/threonine-protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer.