Associations between inflammatory gene polymorphisms (TNF-alpha 308G/A, TNF-alpha 238G/A, TNF-beta 252A/G, TGF-beta 1 29T/C, IL-6 174G/C and IL-10 1082A/G) and osteosarcoma (OS) risk remain unclear. We conducted a systematic search to retrieve studies that investigated associations between inflammatory gene polymorphisms and OS risk. Nine studies that met the inclusion criteria were finally recruited in this meta-analysis. Overall, there was a significant association between TNF-alpha 308G/A, IL-10 1082A/G and OS risk, while there was no significant association between TNF-alpha 238G/A, TNF-beta 252A/G and IL-6 174G/C and OS risk. Our subgroup analysis showed a significant association between IL-6 174G/C and IL-10 1082A/G and OS risk in Asians, while no such significant correlation was observed with TNF-alpha 308G/A, TNF-alpha 238G/A, TNF-beta 252A/G and TGF-beta 1 29T/C polymorphisms. In Caucasians, there was a significant association between TNF-alpha 238G/A and the decreased incidence of OS. In conclusion, inflammatory gene polymorphisms play a key role in the occurrence and progression of OS. IL-6 174G/C polymorphism was obviously associated with OS risk in Asians, while TNF-alpha 238G/A polymorphism seemed to be associated with the decreased susceptibility to OS in Caucasians as Altman and Bland test indicated. Although controversial results were observed between IL-10 1082A/G and OS risk in Asians and Caucasians, it is difficult to make a definite conclusion about the role of IL-10 1082A/G polymorphism in the etiology of OS because our Altman and Bland test showed no good evidence to support a different effect in Asians and Caucasians.