The fruits of Chaenomeles sinensis have numerous therapeutic properties, including anticancer and antiinflammatory activities; however, its antitumor activity and underlying molecular mechanism are poorly understood. The present study evaluated the in vitro and in vivo antitumor activities of a fraction of C. sinensis extract purified on amberlite resin and eluted in 30% methanol (CSAM 30). In vitro, cell viability was assessed using the CCK-8 assay, cell cycle was analyzed by flow cytometry, and apoptosis was measured by Hoechst DNA staining, caspase activity assays and Western blotting. In vivo antitumor efficacy of CSAM 30 was evaluated by oral administration on the human HepG2 hepatocellular carcinoma preclinical xenograft model. In vitro, CSAM 30 inhibited HepG2 cell proliferation and induced apoptosis via activation of caspases, cleavage of poly ADP-ribose polymerase, up-regulation of Bad, and down-regulation of X-linked inhibitor of apoptosis protein XIAP and bcl-2. In vivo, CSAM 30 inhibited HepG2 tumor growth in a dose-dependent manner without inducing body weight loss. These results demonstrate that CSAM 30 induces apoptosis and has antitumor activity in vivo and in vitro.