In this study, we will investigate the interleukin-6 (IL-6) -634C/G polymorphism and the risk of osteosarcoma in the ethnic group Han of China. The subjects in this study consisted of 191 patients with primary sporadic osteosarcoma and 207 cancer-free controls. The IL6-634 G/C polymorphism was determined by PCR followed by restriction fragment-length polymorphism analysis. High risk of osteosarcoma was found in the CG genotype of IL6 -634 G/C polymorphism (OR=1.88, 95% CI 1.23-2.85). However, no significant association was found between GG genotype and osteosarcoma risk (OR=1.62, 95% CI 0.78-2.69). When CG and GG carriers were grouped together, higher osteosarcoma risk was detected (OR=1.81, 95% CI 1.21-2.71). The G allele was significantly associated with risk of osteosarcoma (OR=1.66, 95% CI 1.20-2.28). In conclusion, this study found a significant association between the IL6 -634 G/C polymorphism and osteosarcoma risk.