Objective: To investigate the prevalence and correlation of auto-antibodies in patient with chronic hepatitis C (CHC) and also to investigate the significance of auto-immune reaction in HCV infected patients. Methods: Serum samples were collected from 300 subjects (representing the control and patient groups) visiting King Abdul-Aziz Specialist Hospital in Taif Governorate between June 2017 and December 2017 for detection of HCV by ELISA and RIBA. Serum Antinuclear antibodies (ANA) and Anti-smooth muscle antibodies (ASMA) were detected by IIFT. Result: A total number of 127 (42.3%) of 300 subjects were positive for auto-antibodies. The prevalence rate of ANA was 58 (19.2%) and the prevalence rate of ASMA was 40 (13.3%). While the prevalence rate of ANA and ASMA together was 29 (9.66%). Conclusion: This study denoted that ANA and ASMA are correlated with chronic hepatitis C patients and consider as a marker for autoimmune hepatitis (AIH). They are also more common in females than males patients. Moreover, it can be found in some normal persons.