Background/Aim: The role of hepatitis C virus (HCV) has been demonstrated in many autoimmune diseases, including the autoimmunethyroid disease. However, there is paucity of information about the prevalence of extrahepatic autoimmune phenomenon in HCV-infectedpatients from Egypt and developing countries. This study checked the prevalence of antithyroid autoantibodies in patients with chronic HCVinfection and their possible relation to the human leukocyte antigen (HLA) status.Patients and methods: Sera from 147 consecutive patients (75 males and 72 females) with chronic HCV infection at the Mansoura UniversityHospitals, Egypt during 2008 to 2009, were analyzed for antithyroid antibodies (group 1). A total of 126 anti-HCV positive patients withoutantithyroid antibodies were enrolled as controls (group 2).Thyroid microsomal and thyroglobulin autoantibodies were determined by the hemagglutination tests. IgG type anti-GOR were measuredusing an ELISA assay. HLA-A,-B, -C and -DR were determined using the standard complement-dependent microdroplet lymphocyte cytotoxicitytest.Results: Antithyroid antibodies were detected in 21 HCV RNA positive patients (group 1; 18 females, 3 males) and remaining 126 patients(group 2; 72 males and 54 females). The prevalence of anti-GOR antibodies was significantly higher in patients of group 1 compared to thatof group 2.A statistically significant difference was observed regarding anti-GOR antibodies in group 1 (p < 0.001), antithyroid autoantibodiesamong the females (p < 0.001). HLA-A2 antigen was prevalent in group 1 (p < 0.05).Conclusion: Our data revealed that HLA-A2 may be regarded as an immunologic risk factor for the development of antithyroid autoantibodiesin patients with chronic HCV infection and these autoantibodies should be evaluated prior to initiating IFN-a therapy.Abbreviations: HCV-Hepatitis C virus; IFN-Interferon; HLA-Human leukocyte antigen; ALT-Alanine aminotransferase.