To explore the autoimmune pathogenesis of chronic hepatitis C virus(HCV) infection. Anti-GOR, antinuclear antibodies(ANA), thyroglobulin antibody(TGA), thyroid microsome antibody(TMA), serum levels of soluble Fas(sFas), and peripheral blood lymphocyte(PBMC) subsets and their apoptosis were measured in chronic HCV infection by using immunity assay and flow cytometry, respectively. The results showed that the positive rates of anti-GOR, ANA and TMA/TGA were significantly higher in chronic HCV-infected patients than those in normal controls(P < 0.01, respectively). In comparison with chronic HBV infected patients, anti-GOR and ANA were also significantly increased in chronic HCV infected patients(P < 0.01, P < 0.05, respectively). The serum levels of sFas were significantly higher in chronic HCV infection than those in healthy donors(P < 0.01). The apoptosis percentage of PBMCs and CD3+ cell was all increased in chronic HCV infection (vs normal controls P < 0.05). However, the apoptosis percentages of CD4+ T and CD19+ B cells in PBMCs were significantly decreased in patients with anti-GOR positive as compared with anti-GOR negative(P < 0.01, P < 0.05). The results indicate that autoimmune reactions and the imbalance of lymphocyte apoptosis exist during chronic HCV infection. Decreasing of the apoptosis of CD4+ T and CD19+ B lymphocytes may be the important reasons for the mechanism of autoimmune pathogenesis of chronic HCV infection. Increased serum levels of sFas may be responsible for the decrease of the apoptosis in a part of lymphocytes in chronic HCV infection.