This study designed and synthesized a series of novel ursolic acid derivatives in an attempt to develop potent antitumor agents. Their structures were confirmed using MS, IR, (1)H NMR and (13)C NMR. The inhibitory activities of the title compounds against the MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated using standard MTT assay in vitro. The pharmacological results showed that some of the compounds displayed moderate to high levels of antitumor activities against the tested cancer cell lines and that most exhibited more potent inhibitory activities compared with ursolic acid. The mechanism of compound 4b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, TUNEL assay and flow cytometry, which revealed that the compound can induce cell apoptosis in MGC-803 cells.