Oxyresveratrol (ORES) is a natural phenolic compound with multiple biological functions including antioxidation, anti‑inflammation and neuroprotection; however, the inhibitory effect of ORES on osteosarcoma remains largely unknown. The present study aimed to determine the effects of ORES on osteosarcoma cell Saos‑2. Cell Counting Kit‑8 assay was performed to detect Soas‑2 cell viability. Annexin‑FITC/PI staining and JC‑1 staining were used to measure cell apoptosis and the change of mitochondrial membrane potential. In addition, western blotting was conducted to determine the expression levels of apoptotic proteins and the phosphorylation of STAT3. It was found that ORES inhibited cell viability and induced apoptosis of osteosarcoma Saos‑2 cells in a concentration‑dependent manner. In addition, ORES increased the expression levels of apoptotic proteases caspase‑9 and caspase‑3 and reduced mitochondrial membrane potential. In response to ORES treatment, the expression levels of pro‑apoptotic proteins, Bad and Bax, were enhanced, whereas those of anti‑apoptotic proteins, Bcl‑2 and Bcl‑xL, were reduced. In addition, the phosphorylation of STAT3 was attenuated in Saos‑2 cells after treatment with ORES. Inhibition of cell viability and apoptosis induction by ORES were rescued by enhancement of STAT3 activation upon treatment with IL‑6. Collectively, the present study indicated that ORES induced apoptosis and inhibited cell viability, which may be associated with the inhibition of STAT3 activation; thus, ORES represents a promising agent for treating osteosarcoma.