There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age- and sex-matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence-specific primer method. This study showed the higher frequency of HLA-B*44:02 (P = 0.007), -C*04:01 (P < 0.001), -C*15:02 (P < 0.001) and -C*16:01 (P = 0.027) in the patient group, compared to the controls, while the frequency of HLA-C*06:02 (P < 0.001) and -C*18:01 (P = 0.008) in the patients with pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA-A*03:01, -B*51:01, -C*16:02 haplotype (4% vs 0%,P = 0.04) is suggested to be a predisposing factor, whereas HLA-A*26:01, -B*38, -C*12:03 haplotype (0% vs 6%, P = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA-B*44:02, -C*04:01, -C*15:02 alleles and HLA-A*03:01, -B*51:01, -C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA-C*06:02, -C*18:01 alleles and HLA-A*26:01, -B*38, -C*12:03 haplotype may be considered as protective alleles.