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Objective: To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population., Methods: The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population., Results: The frequencies of HLA-A * 0101 and HLA-DRB1 * 1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4% vs 0.6%, χ 2 =10.788, P =0.001, P c =0.016; 7.5% vs 0%, χ 2 =69.850, P < 0.0001); the frequencies of HLA-DRB1 * 1202 and HLA-DRB1 * 1401 alleles were significantly lower in this patient cohort than in the control group (10.4% vs 16.1%, χ 2 =9.845, P =0.002, P c =0.044; 0% vs 3.1%, χ 2 =18.520, P < 0.001)., Conclusions: The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A * 0101, HLA-DRB1 * 1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1 * 1202, HLA-DRB1 * 1401 and the other 4 alleles can be protective genes in this population.