In this study, we investigated the association between a RECQL genetic polymorphism and osteosarcoma in a Chinese population. We selected rs820196 in the RECQL5 gene and genotyped 185 patients with osteosarcoma and 201 age- and gender-matched non-cancer controls. We found that the CC genotype was more frequent in the osteosarcoma group compared to the control group (P = 0.011). We also found that the C allele was more common in osteosarcoma patients than that in control subjects (P = 0.004). Our results suggested that the RECQL5 genetic polymorphism was associated with osteosarcoma in a Chinese population.