Background: It has been arguedthat unprecedented degree of human leukocyte antigen (HLA) loci polymorphism within a population is requiredto avoid the devastating effects of infectious diseases. The present study was conducted to determine the associations between some of HLA classI genes and the outcome of hepatitis B virus (HBV) infection. Methods: Using sequential sampling method, 64 individuals were selected and categorized into two groups according to their clinical and serological profiles. The patients in the case group were 27 patients with chronic HBV infection and the controls were 37 individuals considered as HBV natural convalescent who recovered from HBV infection. Antibodies againstHBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc) were assessed to exclude primary HBV infection. Individualswith viral clearance were positive for anti-HBs andanti-HBc without the presence of HBsAg at two time points. HLA typing was performed by serological method. Collected data were analyzed by SPSS software version 13. Results: The most frequent HLA antigens among the studied subjects were B51 (40. 1%), B27 (14.1%), B8 (12.5%), and B7 (10.9%). A significant correlation was found between HBV persistence and HLA-B27 (p <0.05). The association between other HLAs (HLA 7, 8, 57) with HBV clearance was not significant. The two studied groups were statistically different in sex but not in age. Conclusion: Findings of the present study demonstrated an association between HLA class I and outcome of HBV infection where HLA B27 was linked to an increase in HBVpersistence. These findings support the hypothesis that HLA class I-restricted cytotoxic T cells play an important role in HBV chronicity.