Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality. HCC is a highly fatal disease as it is the third leading cause of death from malignancy worldwide. The aim of the study was to determine long-term survival and prognostic factors predictive of the overall survival of HCC patients at the National Cancer Institute (NCI), Cairo University. An observational prospective study was conducted on a cohort of 212 HCC patients attending to the medical oncology clinic at the NCI in the period from July,1, 2007 till August, 31,2008 and they were followed up by phone till November 7th, 2010. The study revealed that 1-year, 2-year, 3-year survival rates of HCC patients were 26.9%, 9.4%, 5.0% respectively, and median overall survival was 6.3 months (95% CI 5.4-7.2). Multivariate analysis revealed that independent predictors of worse survival were pretreatment presence of extrahepatic metastasis and ascites, and not receiving radiofrequency ablation (RFA) as a treatment modality. The study concluded that most HCC patients at NCI were presented at a late stage and their survival was poor. Preserved liver function, non metastatic presentation of the hepatic tumor and receiving RFA as a treatment modality were associated with good survival of HCC patients. The study recommends further research studies to be carried out concerning RFA as a treatment modality for HCC, surveillance program to be incorporated into the system of all institutes and centers serving chronic liver disease patients for early detection of HCC.