Background: The outcome of acute hepatitis B infection may be influenced by host genetic factors like human leukocyte antigen (HLA). To investigate the association between the HLA-DRB, DQA1 and DQB1 alleles and chronic hepatitis B infection, 50 patients with chronic hepatitis B (based on 6 months positive of HBsAg and HBc antibody and HBeAg and antibody by serological test), were selected from Turkman population in north east of Iran .Allele frequency in patients were compared with a 65 aged and sex match control group from healthy blood donor of that ethnic population. Methods: HLA DRB, DQA1 and DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP) method. Allele frequencies in patients and control subjects were compared by Epi-info statistical soft-wear. Results: There was a significant increase and positive association in HLA-DRB1*0301, DQA1*0501 and DQB1*0604 allele frequency in patients group while the frequency of HLA-DRB1*1301, 1501 and DQB1*0401 and DQA1*0401, 0102 were lower in patients than control group and shows negative association. Conclusion: In Iranian Torkman population, HLA DRB1*0301, DQA1*0501 and DQB1*0604 have an important role in susceptibility to chronic hepatitis B infection and HLA DRB1*1301, 1501, DQB1*0401 are associated with protection to chronic hepatitis B infection. Larger case control studies may be helpful to confirm our investigation