Background: Hepatitis C virus (HCV) is a major global healthcare problem. The WHO estimates that up to 3% of the world's population has been infected with the virus, equating to more than 170 million individuals worldwide, with significant associated morbidity and mortality. Objective: The aim of this study was to detect effect of treating chronic hepatitis C infection with direct-acting antivirals on the risk of recurrence hepatocellular carcinoma. Subjects and methods: This prospective study included a total of 150 patients with compensated chronic hepatitis C virus infection and 150 patients with compensated chronic hepatitis C virus infection with prior history of treated hepatocellular carcinoma by ablation, resection, chemoembolization or liver transplantation, attending at Viral Hepatitis Units, Departments of Internal Medicine, Assiut and Aswan University Hospitals. This study was conducted between December 2017 and December 2019. Results: The present study shows that 33.3% of HCC had history of treatment with surgical resection, 46.7% had history of Radiofrequency ablation (RFA), 13.3% of Transarterial Chemoembolization (TACE) and 6.7% with liver transplantation. There were highly significant differences between the two studied groups as regard ALT, total bilirubin, creatinine and AFP levels. There were no significant differences between the two studied groups as regard albumin, INR, platelets, total protein and WBCs. There were no significant differences between the studied groups as regard Hepatocellular carcinoma "occurrence or recurrence" and time needed for HCC to occur after direct-acting antiviral agents (DAAs). Conclusion: It could be concluded that antiviral treatment should not be delayed in hepatocellular carcinoma patients in order to avoid further liver deterioration and extrahepatic complications of HCV.