AbstractThe genetic polymorphism of HLA‐A and HLA‐B loci was investigated in 505 Chaoshanese using PCR‐SSP method. Among the HLA‐A alleles detected, A*11 (35.64%) was most frequent, followed by A*02 (31.78%). Of 34 HLA‐B alleles tested, 30 were observed, in which B*60 (21.68%), B*46 (14.46%), and B*58 (10.69%) were highly predominant. Comparison was made with other nine Chinese Han ethnic groups covering the Mainland China, Taiwan, Hong Kong, and Singapore. The high frequent alleles found in Chaoshanese were also common in other Chinese groups compared though the frequency levels varied from group to group. The phylogenic tree analysis based on the HLA‐A and ‐B allele frequencies of all the 10 Chinese ethnic groups revealed that Chaoshanese, while clustering in general with the southern China‐related Han Chinese, had the highest affinity to the Mainland Minnanese, but separated distinctively from the northern Han Chinese. The study, however, was yet to confirm the hypothesis of the Central Plains Han origin of Chaoshanese. Interestingly, the alleles (B*46, B*38, and B*58) and the related haplotypes (A*02‐B*46 and A*33‐B*58) that are positively associated with nasopharyngeal carcinoma (NPC), a disease prevailing predominantly among southern Chinese, were always at much higher frequencies among southern Chinese than among northern Chinese, whereas A*31 and B*13, the two alleles with highly protective effects for NPC, and the associated haplotype A*30‐B*13 were predominantly high in northern Chinese. The different genetic background between northern and southern China may explain, at least partially, the prevalence of NPC among southern Chinese. Am J Phys Anthropol, 2006. © 2006 Wiley‐Liss, Inc.