Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the , , , , , , , and genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.© 2020 The Authors. Published by Elsevier Ltd.