Nasopharyngeal carcinoma (NPC) is characterized by its distinct racial and geographical distribution with a multifactorial etiology. It has been well accepted that NPC is related to Epstein-Barr(EB) virus infection but environmental and genetics factors also play critical roles. Among host genetic markers associated with NPC, the highly variable class I human leukocyte antigen (HLA) genes on chromosome 6 (6p21.3) have shown a strong and consistent association with NPC risk. As the consequence of new generation DNA sequencing technologies used in HLA genotyping, the number of the reported HLA new alleles is dramaticllyincreasing, and more full length sequences of HLA alleles have been reported. The significant association between HLA genes and NPC has been identifiedin a series of studies, including HLA association study, linkage disequilibrium study for microsatellite markers, and genome wide association study. In this review, we summarize association studies between HLA and NPC to evaluate the role of genetic polymorphisms in NPC development and illustrate the new clues of HLA association for deepexploration.