Background: Hepatocellular carcinoma (HCC) is a serious disease that affects people all over the world. It is the second most common cause of cancer mortality in men and the sixth in women. Objective: The aim was to study frequency of Hepatocellular carcinoma in HCV patients treated with direct-acting antiviral drugs. Patients and Methods: The present work was performed on 90 patients. The patients were selected from Oncology Center Mansoura University (OCMU) and specialized medical hospital Mansoura University. The 90 patients were divided into 3 groups: Group 1: 30 HCV-related HCC patients received DAAs previously and in SVR within 2 years of HCC diagnosis. Group 2: 30 HCV-related HCC patients without a previous history of exposure to DAAs. Group 3: 30 patients with chronic HCV (CLD= chronic liver diseases) treated by DAAs without developing HCC within 2 years of treatment and in SVR in addition to a control group of 10 normal persons. Results: BMI was found significantly lower in group 1 compared to group 2 patients. Ascites is more frequent among group 2 than group 1 (43.3% versus 30%, respectively) without statistically significant difference between them. Diabetes history shows statistically significant higher frequency among group 2 than group 3 (53.3% versus 23.3%, respectively). Conclusion: Male gender was predominant among HCC patients even exposed to DAA or not in comparison to group 3 (CLD successfully treated with DAA). A significant increase in HCC patient groups whatever exposed to DAA or not in comparison to HCV CLD patients with SVR as regards ALT, AST, Total bilirubin, INR and AFP, while albumin and Hb levels noticed to be significantly decreased in HCC patients groups in comparison to HCV CLD patients with SVR.