BACKGROUND AND STUDY AIMS: The risk of hepatocarcinogenesis depends on background liver factors, of which fibrosis is a major determinant. Serum markers and scores are of increasing importance in non-invasive diagnosis of hepatic fibrosis. Our aim was to predict the occurrence of hepatocellular carcinoma (HCC) using a non-invasive fibrosis score calculated using routine patient data. PATIENTS AND MTHODS: Our retrospective study included 1,291 hepatitis C related-HCC Egyptian patients (Group 1) recruited from the multidisciplinary HCC clinic, Faculty of Medicine, Cairo University in the period between February 2009 and June 2016 and 1072 chronic hepatitis C-naïve patients (Group 2) with advanced fibrosis (≥F3) and cirrhosis (F4). King score, Fibro Q score, Aspartate aminotransferase-to-platelet ratio index (APRI), AST to ALT ratio (AAR), LOK score, Göteborg University Cirrhosis Index (GUCI), Fibro-α and Biotechnology Research Center (BRC) scores were calculated for all patients. Regression analysis and receiver operating characteristics (ROC) were used to calculate the sensitivity, specificity and predictive values for significant scores with the best cut-off for predicting HCC. A regression equation was used to calculate predicted probabilities of HCC using the following variables; age, gender, haemoglobin, international normalised ratio (INR), albumin and alpha fetoprotein. The appropriate score cut-off points yielding optimal sensitivity and specificity were determined by ROC curve analysis. RESULTS: There was a highly significant difference between the two groups for all calculated scores (P = 0.0001). Our new score, the Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score (Logit probability of HCC =  - 2.524 + 0.152*age - 0.121*Hb - 0.696*INR - 1.059*Alb + 0.022*AFP + 0.976*Sex. Male = 1, Female = 0), with a cut-off of 0.559 was superior to other scores for predicting HCC, having a sensitivity of 90% and specificity of 80.6%. CONCLUSION: The HMC-CU score is a promising, easily calculated, accurate, cost-effective score for HCC prediction in chronic HCV patients with advanced liver fibrosis.