AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m L.CONCLUSION: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients. METHODS: CHB patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (HCC) patients were diagnosed with hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients (AFP) to predict HCC development after interferon Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng / m L before therapy and in non-SVR patients showing AFP ≥ 5 ng / m L before and 1 year after therapy except older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng / m L before therapy and no decrease in AFP to <5 ng / m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng / m L before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng / m L before therapy was significantly associated with low platelet counts and high values ​​of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count , and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP <5 ng / m L before therapy than in showing either AFP ≥ 5 ng / m L. CONCLUSION: The criteria of AFP <5 ng / m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.