Background:  Management   of chronic infection with hepatitis C virus (HCV) with direct acting antivirals (DAAs) agents achieves high virological response. Recently, there is a matter of controversy about occurrence of hepatocellular carcinoma (HCC) following those agents. Objective: This study aimed to evaluate the efficacy of alpha fetoprotein (AFP) in development of HCC following DAAs therapy.  Patients and methods: two hundred patients with chronic HCV infection who were eligible for DAAs therapy were recruited. Those patients were followed up for one year following therapy to detect development of HCC. Patients were grouped into either with normal AFP (100 patients) or high AFP (100 patients). Results: Majority (84%) of patients were males with overall mean age of 43.87±12.76 years. There were no significant differences between both groups of patients as regard baseline data. With exception of 4% of patients, all of them reached the sustained virological response (SVR). Frequency of HCC detection was higher among those patients with high AFP (9 (9%) vs 1 (1%); P< 0.001). We found that liver cirrhosis; FIB-4, APRI and AFP were predictors for HCC. AFP had the best diagnostic accuracy for prediction of HCC following DAAs Conclusion: Patients who received DAAs for HCV infection should be regularly screened for development of HCC.