The frequencies of the human leukocyte antigen alleles HLA-A, HLA-B, and HLA-DRB1 and the A-B-DRB1, A-B, and B-DRB1 haplotypes were studied in Naxi and Yunnan Han populations using polymerase chain reaction (PCR)-sequence-specific amplification for alleles A and B and a PCR-microtiter plate hybridization method for the DRB1 allele. A total of 8 A, 19 B, and 30 DRB1 alleles were found in the Naxi population, and 15 A, 21 B, and 36 DRB1 alleles were found in Yunnan Han population. The common A-B-DRB1 haplotypes in the Naxi population were A*24-B*15-DRB1*1202, A*11-B*15-DRB1*0405, A*11-B*15-DRB1*1202, A*11-B*38-DRB1*08032, and A*11-B*55-DRB1*0405; the common A-B haplotypes were A*11-B*15, A*11-B*38, and A*24-B*15; and the common B-DRB1 haplotypes were B*15-DRB1*1202, B*38-DRB1*08032, and B*48-DRB1*1201. In the Yunnan Han population, the common A-B-DRB1 haplotypes were A*24-B*15-DRB1*1501, A*24-B*46-DRB1*08032, and A*24-B*15-DRB1*1201; the common A-B haplotypes were A*24-B*15, A*24-B*46, and A*34-B*46; and the common B-DRB1 haplotypes were B*15-DRB1*1501, B*46-DRB1*09012, and B*46-DRB1*1401. Phylogenetic tree and principal component analyzes based on HLA-A, HLA-B, and DRB1 allele frequencies suggested that the Naxi ethnic group belongs to the southern Chinese groups, while the Yunnan Han population is a characteristic population located intermediate between northern and southern Chinese groups, although they live in the southwest of China.