Abstract: 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 HLADRB1 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%, χ2=10.788, P=0.001, Pc=0.016; 7.5% vs 0%, χ2=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%, χ2=9.845, P=0.002, Pc=0.044; 0% vs 3.1%, χ2=18.520, P<0.001). Conclusion 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.