Hashimoto's thyroiditis (HT) is a complex genetic autoimmune thyroid disease (AITD). Thyroid-stimulating hormone receptor (TSHR) is considered as candidate gene in AITD. IL1RN gene is involved in the pathogenesis of a number of autoimmune diseases. These findings prompted us to investigate the association of TSHR and IL1RN genes polymorphism with the risk and the prognosis of HT in Tunisia. A total of 249 healthy controls and 202 patients with HT were genotyped for TSHR D727E and IL1RN(VNTR) polymorphism. No significant difference was found for D727E polymorphism between HT patients and healthy controls. For IL1RN gene, we found an association between HT and IL1RN(VNTR) polymorphism. The A1A3 genotype was more prevalent in HT patients than in controls. However, the A1A4 genotype was associated with HT as a protective factor. Significant association of the TSHR polymorphism with lower plasma TSH level in HT patients has been detected. We found for the first time an association of IL1RN(VNTR) polymorphism with the production of anti-thyroid peroxidase antibody at the onset of disease. These preliminary results suggest that only the IL1RN(VNTR) polymorphism may be associated with HT susceptibility and that TSHR and IL1RN(VNTR) polymorphisms may represent prognostic factors for predicting the severity of HT.