Background: Alopecia areata(AA) is a common autoimmune disease that causes hair loss without scarring. It occurs as a result of T-helper 1 (Th1) and Th17 cells attacking the anagen hair follicles. Genetic factors play a role in the occurrence of infection, which stimulates the production of pro and anti-inflammatory interleukins. Polymorphisms of IL-37 play a role in autoimmune diseases. However, IL37 single nucleotide polymorphisms(SNP) have not been identified in patients with AA. Therefore, this study aimed to reveal the IL37 gene SNP and its relationship to AA. Methods: Genotyping of IL-37 gene single nucleotide polymorphisms SNPs were detected using sequence-specific primer-polymerase chain reaction (SSP-PCR) method was done following the protocol of DNA Extraction kit and PCR PreMix SNP Genotyping Assays in 51 (32 males & 19 females at age mean 27.90±1.66 years) patients with AA and 50 (21 males & 29 females at age mean30.64±2.08years ) healthy individuals. Results: The results of the present study showed a significant increase in the mean level of IL-37 in the serum of patients with AA compared to healthy subjects (184.18±69.45 vs.153.28±48.17) pg/ml. This increase did not constitute a significant difference at a probability level less than. In addition, genotypes of single nucleotide polymorphisms (SNPs) of IL-37 gene were rs3811045 (5756 T>C) and rs3811046 (5831 G>T) that result in substitution and inversion mutations, and thus cause a change in the type of amino acid. The CC and allele C and TC of rs3811045 were risk factors for AA due to a significantly higher odd ration (OR) value and a significantly increased frequency percentage in patients group compared to a healthy control group (37.50 vs 25.58 OR: 1.75 p = 0.264, 95% CI = 0.72–4.25, 66.0 vs 86.0 OR: 1.78 p = 0.068, 95% CI = 0.98–3.23; 56.25 vs 55.81 OR: 1.02 p = 1.0 95% CI = 0.45–2.31 respectively). Also the results of rs3811046 recorded that the TT and allele T frequency percentages were significant increase in patients group (39.58 vs 25.58 OR: 1.91 P = 0.184, 95% CI = 0.79-4.63, 66.0 vs. 52.0 OR: 1.74, P =0.072,95%CI= 0.96–3.15) respectively, which was a risk factor for infection. This study is the first of its kind to show the relationship of IL-37 level and genetic single nucleotide polymorphisms with AA. Conclusions The present study's results can conclude that the TC, CC and the C allele of IL-37 SNP rs3811045 and TT genotypes and the T allele of IL-37 SNP rs3811046 have a role in the risk of developing AA. It is recommended to conduct several genetic studies of other interleukin genes and to ascertain their relationship to AA. © 2023, Journal of Biomechanical Science and Engineering.