Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and it`s prevalence in Egypt has been rising in the last few years. The aim was to study determinants of HCC in Clinical Oncology and Nuclear Medicine Department in Zagazig University Hospitals. Methods: This is a retrospective chart review of 538 patients with HCC conducted from 2012 to 2017. Analysis of data in files was done to study the determinants of HCC. Results: The majority of cases (77%) were male, about 71.7% of patients were from urban areas. Age of majority of cases was in 50s (40%). (99.71%) of patients were of cirrhotic liver. HCV antibody was detected in serum of (89.92%) of studied cases while hepatitis B virus infection was detected in only (3.10%) of cases. Conclusion: HCC is a major health problem in Zagazig and its incidence is increasing. The high prevalence of HCV infection makes screening programs and following up of HCV patients is a very important tool for early detection of mild HCCs cases.