Hypothyroidism is a frequent disorder in the general population, especially among women, is defined as adeficiency of thyroid activity that results from insufficient production or action of thyroid hormones leading to a totaldecrease of metabolic. Human leukocyte antigen is the most polymorphic genetic system in man. Genes of this regioninfluence susceptibility to certain diseases.Objectives: The purpose of the present study is to investigate the role of HLA-DRB1 genotyping in hypothyroidpatients with and without periodontitis. Sixty hypothyroid patients 30 of patients were with periodontitis and 30without periodontitis compare with 30 healthy subjects as control enrolled in this study. DNA was extracted fromblood samples, then HLA- genotyping performed by polymerase chain reaction-sequence specific oligonucleotideprobes (PCR-SSO). The results showed the frequencies of HLA-DRB1*03 and *04 alleles are significantly increasedin hypothyroid patients than control (P<0.001; P<0.05) respectively; whereas, the frequencies of HLA-DRB1*08allele is significantly higher in control group as compared to patients group (P<0.05). Surprisingly comparisonbetween groups of hypothyroid patients with and without periodontitis revealed significant higher frequency (P<0.05)of DRB1*03 allele among group of hypothyroid patients with periodontitis. The present findings suggested that thepresence of HLA-DRB1*03 and HLA-DRB1*04 alleles may increase the susceptibility to hypothyroidism, whileHLA-DRB1*08 allele could confer protective effects against this disease. Moreover, patients with HLA-DRB1*03allele are more likely to develop periodontitis