Glioma is the most common type of primary brain malignancy in adults. The X-ray repair cross-complementing group 1 (XRCC1) is an important candidate gene for influencing the pathogenesis of glioma. This study aimed to evaluate the potential association between XRCC1 genetic polymorphisms and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 620 glioma cases and 630 cancer-free controls. XRCC1 genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and verified using DNA sequencing methods. The c.910A>G and c.1779C>G genetic polymorphisms were identified in this study. Our data suggested that the genotypes/alleles of these two genetic polymorphisms were statistically associated with the increased risk of glioma. As for c.910A>G, the risk of glioma for genotype GG was significantly higher than wild genotype AA (odds ratio (OR) = 1.98, 95% confidence interval (CI) 1.33-2.94, P = 0.001). As for c.1779C>G, the genotype GG was statistically associated with the increased risk of glioma compared to wild genotype CC (OR = 1.80, 95% CI 1.17-2.78, P = 0.007). Both of alleles G in c.910A>G and c.1779C>G may contribute to glioma susceptibility (G versus (vs.) A, OR = 1.30, 95% CI 1.09-1.54, P = 0.003; G vs. C, OR = 1.19, 95% CI 1.00-1.42, P = 0.045). Our findings indicate that the c.910A>G and c.1779C>G genetic polymorphisms are associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.