Hepatitis C Virus (HCV) RNA detection has been used for the management decision and efficacy of therapy in chronic HCV infection. The aim of the present study was to investigate any possible interaction between HCV RNA and autoantibodies in order to use autoantibodies for management decision and efficacy of therapy in chronic HCV infection. For this purpose, a panel consisting 234 anti-HCV positive and 51 anti-HCV negative sera were formed. With all sera HCV RNA, anti-nuclear (ANA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomal (LKM) autoantibody tests were performed. Hepatitis C virus RNA genotype was detected. While ANA was found to be positive at a dilution of 1:100 in 32.4% of HCV RNA negative, it was 16.0% in HCV RNA positive sera. According to the logistic regression analysis, the presence of ANA was found to be affected by the HCV RNA status. Hepatitis C virus RNA is valuable to show the efficacy of antiviral therapy in chronic HCV infection. The data provided by this study lead to raise an idea of using ANA for showing efficacy of antiviral therapy in chronic HCV infection.