Objective:To assess the association of DNA double-strand break repair genes XRCC5 and LIG4 with glioma. Methods:126 patients with glioma (case group) and 120 healthy volunteers (control group) were enrolled. The polymorphisms of XRCC5 loci rs828704 and rs9288516, LIG4 loci rs3093737, rs3093739 and rs10131 were detected, and their association with the susceptibility to glioma was analyzed. Results:Hardy-Weinberg test showed that XRCC5 loci rs828704 and rs9288516, LIG4 loci rs3093737, rs3093739 and rs10131 were in equilibrium in both groups ( P>0.05). The frequency of A allele of XRCC5 gene rs9288516 locus and T allele of LIG4 gene rs10131 locus in the case group was higher than that in the control group ( P<0.05). XRCC5 rs9288516 and LIG4 rs10131 were associated with the susceptibility to glioma under both recessive and additive models ( P<0.05), while LIG4 rs3093739 was associated with susceptibility to glioma under the recessive model ( P<0.05). Conclusion:XRCC5 rs9288516 and LIG4 rs10131 are associated with the susceptibility to glioma. Above finding may provide a reference for the prevention and treatment of glioma.