Abstract: The polymorphism of HL A-B alleles in Sichuan Yi and Xinjiang Uygur population were investigated using the PCR-SSP method. Twenty alleles were detected in HLA-B loci in 106 Sichuan unrelated Yi healthy subjects. Of them, B*40, B*15 and B*51 were the most common alleles with an allele frequency of 0.2208, 0.1604, 0.1274 respectively; B*47, B*27, B*44, B*18 and B*78 were the rare alleles with an allele frequency of 0.0189, 0.0142, 0.0142, 0.0094 and 0.0047 respectively. In 110 Xinjiang unrelated healthy Uygur subjects, 27 alleles were detected in HLA-B loci. Of them, B*35 and B*51 were the most common alleles with an allele frequency of 0.1136 and 0.1136 respectively; B*41, B*56 and B*78 were the rare alleles with a frequency of 0.0045, 0.0045 and 0.0091 respectively. The result of χ2 tests showed that the distributions of HLA-B alleles in Yi and Uygur ethnic groups were in Hardy-Weinberg equilibrium. Heterozygosity (H), discrimination power (DP) and probability of paternity exclusion (EP) of HLA-B locus from Sichuan Yi ethnic group were computed to be 0.8977, 0.9661 and 0.8009; and those from Xinjiang Uygur ethnic group as 0.9372, 0.9857 and 0.8732. This study obtained data on the distributions of HL A-B alleles in the Sichuan Yi and Xinjiang Uygur population and the data can be used in forensic and paternity tests to estimate the frequency of a DNA profile in these two populations, transplant matching, anthropology and disease association study.