The pathogenesis of nasopharyngeal carcinoma (NPC) is multifactorial. Associations have been reported between HLA and NPC. We studied the HLA-DR and -DQ regions on the molecular level in 136 persons (51 NPC patients and 85 healthy controls) from southern China, a particularly high-prevalence area for NPC. Restriction fragment-length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha, and DQ beta regions of the subjects. Polymerase chain reaction (PCR) using sequence-specific primer (SSP) for DQ beta genes was also performed. By RFLP, no significant difference was observed with respect to DRB, DQA, and DQB genes. By PCR SSP typing, we confirmed that there was no significant difference between NPC patients and controls with respect to DQ beta alleles. Our study suggests that HLA-DQ and -DR genes are not associated with NPC in southern Chinese and there may be other gene loci that predispose them to have such a high prevalence of the disease.