Background: Egypt had been vexed by the highest load of chronic hepatitis C in the world. It represents a vast market of the new direct-acting anti-viral drugs (DAAs); effectively treating chronic hepatitis C virus (HCV) infection. Objectives: The aim of this study is to detect the occurrence and recurrence of hepatocellular carcinoma (HCC) during the follow-up after antiviral treatment with direct acting antiviral therapy in patients with chronic HCV infection and in patient with chronic HCV prior history of treated hepatocellular carcinoma who achieved complete response. Subjects and methods: This was prospective study including 150 patients with compensated chronic hepatitis C virus infection and 150 patients with compensated chronic hepatitis C virus infection prior history of treated hepatocellular carcinoma. The patients were attending Aswan university hospital and viral hepatitis unit in addition to Viral Hepatitis Unit and were prospectively collected at the end of December 2019. The patients were divided into two groups: Group (A): patients with chronic HCV infection who were treated with direct acting antivirals. Group (B): patients with chronic HCV infection prior history of treated hepatocellular carcinoma who were treated with direct acting antivirals. Results: The results of the study revealed that there was no significant difference between the studied groups as regard time needed for HCC to occur after DAA. Conclusion: Surveillance programs should be widely endorsed during and after DAAs therapy for patients at HCC risk, even for those who had been achieved HCV cure.