Objective: Papillary thyroid carcinoma (PTC) is the most frequent types of thyroid malignancies. Several genes may be involved in susceptibility of thyroid cancer including Human Leukocyte Antigens (HLA). The association of thyroid carcinoma with HLA alleles has been previously studied in other populations and certain HLA alleles were shown to be either predisposing or protective. The aim of this study was to determine the association between HLA-DR and papillary thyroid carcinoma in an Iranian population.Design: HLA-DR antigen frequencies were determined in patients with papillary thyroid carcinoma (N = 70) and non-related healthy controls (N=180) using PCR -SSP.Main Outcome: We found that HLA-DRB1*04 frequency was significantly higher in our patients compared to the controls [P = 0.02, OR; 1.9, 95% CI (1.04–3.57)].Conclusions: Our results revealed HLA-DRB1*04 as predisposing factor in papillary thyroid carcinoma in Iranian population. This confirms the previous findings for associations between HLA-DRB1 and differentiated carcinomas in other populations.