Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. The burden of HCC has been increasing in Egypt. Most HCC are diagnosed at intermediate or advanced stages beyond any curative therapies.Serum AFP has a low sensitivity, and about one third of early stage HCC patients have low level of AFP. HCC is a hypervascular tumor and vascular endothelial growth factor (VEGF) is pathogenically involved in HCC. We aimed to evaluate the clinical usefulness of VEGF and HCC-VEGF score in the diagnosis of HCC. The study was conducted on 89 subjects including 34 patients with HCC, 35 patients with HCV related liver disease and 20 healthy controls. Full history taking, clinical examination, routine laboratory and radiological investigations were done. Serum VEGF and AFP were measured.HCC was presented more in males. AFP and VEGF levels were significantly higher in HCC group than in cirrhotic group. HCC-VEGF score was significantly higher in patients with HCC group with a mean value of 11.96±10.40 compared to 1.24±1.32 in cirrhotic group and -2.73±0.53 in healthy controls (p< 0.001). HCC-VEGF score was positively correlated with size of hepatic focal lesion whereas it showed no statistically significant correlation with Child-Pugh score or MELD score. HCC-VEGF score at a cutoff point of 2.59 showed a sensitivity and specificity of 100 and 82.86 % respectively with area under the curve 0.97. So , VEGF and HCC-VEGF score may represent a non invasive marker for prediction of HCC in patients with chronic HCV related liver disease.