Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1*06 (OR = 1.67, 95% CI = 1.17–2.39) and DRB1*13 (OR = 1.69, 95% CI = 1.08–2.64) alleles were associated with an increased risk of glioma, while the DQB1*05 allele showed an inverse association (OR = 0.63, 95% CI = 0.43–0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1*06 , DQB1*05 , and DRB1*13 alleles in glioma susceptibility.