Abstract: Objective To investigate clinical characteristics and predictive factors of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) receiving IFN-α based treatment. Methods Four hundred and thirty-two consecutive CHC patients with normal baseline thyroid functions who received IFN-α based therapy in our hospital from October 2013 to April 2014 were enrolled in this study. There were 259 males (60.0%) and 173 females (40.0%) with an average age of (43.5±32.7) years. Thyroid and liver function, TPOAb, TGAb, HCV RNA and HCV RNA types before and 3, 6, 9, 12 months after treatment were detected by Chemiluminescence, enzymatic and fluorescent quantitative PCR technology, respectively. Results At the end of IFN-α based therapy, 67 patients (15.5%) in this study had developed with TD while the hypothyroidism patients took the most. The percentage of hypothyroidism accounted for 58.2%. The incidence of this disease in female was higher than male with male to female ratio of 3.8 ∶ 1. The cumulative incidence at three, six months after initiation of IFN-α based HCV treatment was 47.8% (32 patients) and 86.6% (58 patients), respectively. The thyroid function of 63 patients (74.6%) spontaneously returned to normal in the followup period of 12 months and only 4 patients (6%) had persistent overt TD symptoms. Multivariate stepwise analysis suggested that gender and pretreatment TPOAb, TGAb were the independent factors related to the incidence of TD. Conclusion The incidence of TD in patients with CHC during IFN-α based therapy is 15.5%, taking female as the main. Female gender, pretreatment TPOAb and TGAb positivity are risk factors for the development of TD during IFN-α based therapy.