Cancer prevention includes approaches that can reduce the risk of developing cancer, such as maintaining a healthy diet and avoiding exposure to mutagenic agents. Plants with antimutagenic properties can be valuable as cancer-protective agents. This study aims to investigate the antimutagenic activity and cancer-protective effects of Ziziphus spina-christi using in vitro and in vivo human and animal models, respectively. The antimutagenic activity of Ziziphus spina-christi leaf extract was examined in cultured human lymphocytes using sisterchromatid exchanges (SCEs) and 8-OHdG assays. In addition, the cancer-protective effect of the extract was investigated using a skin painting assay and7,12-dimethylbenz(a) anthracene (DMBA)induced cancer of Balb/c mice. Animals were treated with DMBA for 20 weeks with concurrent consumption of Ziziphus spina-christi leaf extract 100mg/kg daily, 5 days/week. The Ziziphus spina-christi leaf extract significantly reduced the levels of SCEs and the 8-OHdG levels in human lymphocytes in a dose-response manner (P0.05). In conclusion, the experimental investigation demonstrated the beneficial properties of Ziziphus spina-christi as an anticancer agent.