Background: Hepatocellular carcinoma (HCC) is the fourth most prevalent cancer in Egypt. The use of direct-acting antivirals (DAAs) has come under attention recently due to concerns about increased HCC risk. Objective: The aim of the current work was to determine the frequency of HCC after treatment of hepatitis C virus (HCV) by DAAs. Patients and Methods: This retrospective cohort study included a total of 69 Egyptian patients with HCV. It was performed from the registered patients' records, Faculty of Medicine, Zagazig University Hospitals. Patients were treated using direct-acting antivirals (DAAs) and had sustained virological response after twelve weeks (SVR 12), a follow-up over the course of subsequent six months to detect HCC occurrence. Abdominal ultrasound screening and serum alpha-fetoprotein level after completion of DAAs treatment was done every three months. Any suspicious lesion in the liver was further confirmed by Triphasic CT Scan. Results: HCC incidence was 10.4%. Cases with a Child-Pugh score A were not more likely to develop HCC after completing treatment, and SVR12 was not associated with an increased risk of HCC, though, the patients with a ChildPugh score B were at high risk (P = 0.0001). Treatment with SOF+DAC for 24 weeks was associated with a risk of HCC incidence (p 0.0001). Prolonged prothrombin time and the incidence of an unfavorable effect of DAAs (fatigue and gastrointestinal troubles) emerged as HCC development independent risk factors in a multivariate analysis with OR (CI) of 16.8 (10.2-78.6), 15 (1.16-73.7), 19 (1.48-46.6) respectively. Conclusion: HCC following DAAs treatment still occurs in certain patients, especially with advanced liver cirrhosis. Prolonged prothrombin time and DAAs-related side effects are independent risk factors for HCC.