b-Ionone is a constituent of vegetables and fruits, and can induce apoptosis in some types of malignant cells. However, the mechanism of apoptosis in osteosarcoma (U2os) cells is currently unclear. In this study, we determined whether b-ionone can induce apoptosis in U2os cells in vitro and which signal pathway(s) is involved. We found that b-ionone inhibited cell proliferation in U2os cells in a concentration- and time-dependent manner and caused cell cycle arrest at the G1-S phase. TUNEL assay, DNA ladder and assessment of Caspase 3 activity showed that apoptosis was the determinant in the effects of b-ionone. Furthermore, Expression of the p53 protein increased in a concentration-dependent and time-dependent manner according to immunocytochemistry and immunoblotting after b-ionone treatment. In addition, b-ionone upregulated Bax protein and downregulated Bcl2 protein which led to Bax translocation and cytochrome c release, subsequently activated Caspase 3, thus resulting in apoptosis. In summary, these data suggested that b-ionone induced apoptosis in a concentration-dependent manner in U2os cells via a p53-dependent mitochondrial pathway.