The human leukocyte antigens (HLA) DRB1 polymorphism has been implicated in susceptibility to nasopharyngeal carcinoma (NPC). However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the HLA-DRB1 polymorphisms and NPC risk. All eligible case-control studies published up to June 17, 2015 were identified by searching PubMed, Web of Science, CNKI, Wanfang, and Weipu databases. The NPC risk associated with the HLA-DRB1 polymorphism was estimated for each study by odds ratios (OR) together with its 95 % confidence interval (CI), respectively. Twelve studies with 1152 cases and 1600 controls were included. Overall, a significant positively association between the HLA-DRB1*03, *08, *09, and *10 alleles polymorphism and NPC risk were found (OR = 1.55, 95 % CI 1.30-1.86; OR = 1.44, 95 % CI 1.08-1.92; OR = 1.33, 95 % CI 1.06-1.67; OR = 1.82, 95 % CI 1.02-3.26, respectively), and the HLA-DRB1*01, *11, and *12 alleles were negatively associated with NPC risk (OR = 0.55, 95 % CI 0.39-0.78; OR = 0.62, 95 % CI 0.42-0.91; OR = 0.62, 95 % CI 0.47-0.81, respectively), but we failed to detect any association between other alleles and NPC risk. When stratified by ethnicity, similar results were observed among Asians for HLA-DRB1*03, *08, *09, *11, and *12 alleles and Tunisians for HLA-DRB1*01, *03, and *11 alleles; However, no significant association among Caucasians was observed. This meta-analysis suggests that the HLA-DRB1*03, *08, *09, and *10 alleles polymorphism contributed to the susceptibility of NPC, whereas HLA-DRB1*11 and *12 alleles polymorphism may be an important protective factor for NPC, especially of Asian populations. [ABSTRACT FROM AUTHOR]