Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) A49G is a polymorphism that is extensively studied in various cancers. To investigate whether it is associated with the occurrence of glioma in Chinese patients, we performed a case-control research study with 670 patients and 680 controls. In this group, we found that the genotype at this locus is significantly associated with glioma risk (GG vs. AA: P = 0.045; GG + AG vs. AA: P = 0.013). In some subgroups, G allele carriers are significantly less represented. We also observed significant correlations between the polymorphism genotype and glioma risk in patients with WHO histologic stages. We conclude that CTLA4 A49G might be a potential clinical biomarker for distinguishing persons with a high risk for developing gliomas.