Aim: To compare changes in AFP levels before and after interferon treatment in responders and non-responders with liver histopathological changes and to verify the possibility of using AFP as a predictor of response to interferon-ribavirin therapy in chronic HCV genotype 4 patients. Background and methods: HCV infection is a major health problem in Egypt and it is a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to HCC. AFP has been widely used as a diagnostic marker for HCC. Elevated levels of AFP can be seen in chronic HCV. This prospective study recruited 79 chronic HCV patients (genotype 4) who received treatment in the form of PEG-IFN alfa-2b 100 µg weekly and ribavirin 11mg/kg/day for 48 weeks then followed up by AFP level and liver biopsy. Results: AFP level decreased in all patients with better results in SVR patients. Histopathological improvements occurred in most patients after treatment. Pre-treatment AFP was correlated with age, fibrosis, inflammation, transaminases, hemoglobin, platelet count and AFP difference. Conclusions: AFP can be used as a good predictor for treatment response before starting treatment in chronic HCV genotype 4 patients.