Three polymorphisms of X-ray repair cross-complementing groups 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln may be associated with the individual susceptibility to glioma. The aim of this study was to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280, and 399 and potential glioma risk. We conducted a hospital-based case-control study in northwest China. A total of 1,772 subjects, including 886 glioma patients and 886 healthy controls, were recruited in this study. The peripheral blood samples were extracted. Polymerase chain reaction-restriction fragment length polymorphism method was used to test genotypes. Glioma patients had a significantly higher frequency of XRCC1 194 TT (odds ratio [OR] = 1.76, 95 % confidence interval [CI] = 1.14, 2.72; P = 0.01) and XRCC1 399 AA genotype (OR = 1.62, 95 % CI = 1.09, 2.40; P = 0.02) than controls. When stratified by the grade of glioma, patients with WHO IV glioma had a significantly higher frequency of XRCC1 194 TT (OR = 1.60, 95 % CI = 1.02, 2.51; P = 0.04) and XRCC1 399 AA genotype (OR = 1.59, 95 % CI = 1.04, 2.42; P = 0.03). When stratified by the histology of glioma, there was no significant difference in the distribution of each genotype. This study suggested that XRCC1 Arg194Trp and Arg399Gln polymorphisms were associated with the risk of glioma.