Background and study aim : The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. Hepatitis C virus infection plays an important role in the pathogenesis of immunological derangement, but the mechanism remains unclear. The aim of this study is to detect the significance of ANA positivity and its impact on histopathology and early virological response (EVR) to combined antiviral therapy in chronic HCV patients. . Patients and Methods:Two hundred Egyptian chronic HCV naïve patients were enrolled in this study. Antinuclear antibody (ANA) was detected by ELISA and it was considered positive with a titer > 1 : 14 by indirect immunofluorescence. Complete laboratory investigations and histological examination were done as a pretreatment work up for all patients. Patients were followed up during treatment and EVR was assessed in ANA positive and negative patients. Results: There was a statistically significant difference between ANA positive and negative patients regarding viral load and histopathological criteria and no significant difference was detected regarding other demographic and laboratory criteria. EVR was close in ANA positive and ANA negative patients (77 for the former Vs. 80 for the later with P = 0.33). No autoimmune manifestations were detected during treatment among positive cases. Except for ALT & AST levels no statistically significant differences were detected between ANA positive and negative cases regarding haematological data, thyroid dysfunction. BMI, ALT levels, viral load and fibrosis stages were independent predictors of EVR. Conclusion: ANA postivity in chronic HCV patients was associated with advanced fibrosis but didn't affect treatment response.