Background: Thyroid disease is a common disease in women of the reproductive age. This disease arises due to complex interactions between environmental and genetic factors. However, the interactions between genes and environment are yet well defined. Among the main susceptibility genes that have been identified is the HLA-DQB1 gene locus. The major environmental factors include iodine, medications, infection, smoking, and possibly stress. Aim of study: To ascertain the association between HLA-DQB1 alleles and goitrous thyroid disease in a sample of Iraqi Arab Muslims. Patients and methods: A cross sectional case-control comparative study was carried out. Patients with thyroid disorders who attended this hospital in the period from September 2013 to June 2014 for thyroidectomy were studied. HLA-DQB1genotyping was done using a panel of sequence-specific oligonucleotide probes (SSOP) using HLA-DQB1 amplification and hybridization kits (SSO HLA type DQB1 plus and Mastermix for HLA type DQB1 Amp plus) using automated method by AutoLipa-48. Results: There was an increased frequency of HLADQB1*03:01and 0601 in control group compared with patients group (P=0.005, Odds ratio=0.0164, 95% CI: 0.0009-0.2926) and (P=0.01, Odd ratio=0.1667, 95% CI: 0.0412 to 0.6750) respectively. Other alleles like HLA-DQB1* 0202, 03:02, 0501 and 06:02 were detected in the patients' group but not in controls. Conclusions: HLA alleles have an effect on development thyroid disease. HLADQB1* 0301 and 0601 is a protective in Iraqi Arab Muslims individuals.