Background. Hepatitis C virus (HCV) infection is a leading cause of liver cancer globally. Treating chronic HCV with direct-acting antivirals (DAAs) in cirrhotic patients has raised concerns about their effect on HCC development and progr-ession. Objective: To compare the characteristics of de novo HCC in chronic HCV cirrhotic patients who achieved susta-ined virological response (SVR) with DAAs therapy, with that of HCC which developed in chronic HCV cirrhotic patients who did not receive DAAs or PEG interferon-based treatments. Methods The study included 200 chronic HCV cirrhotic patients divided into two groups: group 1 with 100 patients who developed de novo HCC post-SVR following DAAs, and group 2 with 100 HCV-related HCC patients who developed HCC without prior antiviral therapy. Non-invasive HCC diagnosis was based on EASL guidelines. Baseline demogr-aphic, clinical, and laboratory data were collected. The Child-Turcotte-Pugh (CTP) score, class, and Barcelona Clinic Liver Cancer (BCLC) staging system were determined (stages 0/A as early stages, while BCLC stages B/C/D as late stages of HCC). The types of DAAs used for chronic HCV treatment were also recorded. Results. Post-DAAs HCC was diagnosed approximately 4.3 years post-SVR, characterized by multi-focal or diffuse infiltration compared to HCV-related HCC. The tumor diameter in post-DAAs HCC was larger versus in HCV-related HCC (p= 0.002). Linear regression analysis indicated that DAAs therapy was a significant predictor of a larger tumor diameter. Malignant portal vein thrombosis (PVT) was more prevalent in post-DAAs HCC compared to HCV-related HCC (p= 0.001). CTP score was significantly lower in post-DAAs HCC compared to HCV-related HCC (p < .001). Post-DAAs HCC was diagnosed at later BCLC stages than HCV-related HCC. The serum AFP level was insignificantly higher in post-DAAs HCC than in HCV-related HCC. Platelets were significantly higher in post-DAAs HCC than in HCV-related HCC (p= 0.001). ALT levels were significantly lower in post-DAAs HCC compared to HCV-related HCC (p=0.02). Conclusion Post-DAAs HCC had larger size, a more diffuse pattern, and a higher rate of malignant PVT compared to HCV-related HCC. It was diagnosed at later BCLC stages but had lower CTP scores, lower ALT levels, and higher platelet counts.