BACKGROUND: Hepatitis C virus (HCV) infection may induce autoimmune response and autoantibodies can be detected in chronic hepatitis C (CHC) patients. However, the reported positive rate of autoantibodies in CHC patients in China varies considerably. In this study, we investigated the prevalence of antinuclear antibodies (ANA) and anti-liver-kidney-microsome type 1 autoantibodies (anti-LKM-1) in a large cohort of CHC patients, and analyzed the factors related to the presence of the autoantibodies. METHODS: A total of 360 CHC patients were enrolled in this study. Serum ANA and anti-LKM-1 were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively. Clinical analysis was performed to disclose the related factors to autoantibody production. RESULTS: The prevalence of ANA and anti-LKM-1 in CHC patients was 12.5% (45/360) and 2.5% (9/360), respectively. Women had a higher prevalence than men (18.9% vs 11.4%, P = 0.046). Patients with positive autoantibodies had lower HCV RNA levels (1.2 x 10(7) copies/L vs 7.2 x 10(7) copies/L, P < 0.05). Positive ANA was associated with higher serum globulin (P < 0.05). Stratified analysis showed that there were no significant differences in age, HCV genotype, disease course, clinical stage, prevalence of cirrhosis and interferon therapy between autoantibody-positive and -negative subgroups. CONCLUSION: Autoantibodies can be induced in the course of CHC, and some CHC patients can even develop autoimmune hepatitis.