Background and Objectives:Hepatocellular carcinoma (HCC) is a typically hypervascular tumor and ranks as the fifth most common cancer around the world and the third most frequent cause of cancer-related death. Vascular endothelial growth factor (VEGF) has been reported to play an important role in the angiogenesis of HCC. This study is designed to investigate the expression of VEGF in HCC and its relation to clinico-pathological characteristics of HCC and to compare VEGF expression in surrounding non-tumorous liver tissue, HCV-related chronic hepatitis and cirrhosis. Methods:Immuohistochemistry was performed to investigate the expression of VEGF proteins in liver tissues from 80 Egyptian patients (28 cases of surgically resected HCC, and needle biopsies from 20 cases of HCV-related chronic hepatitis and 20 cases of HCV-related cirrhosis, and 12 control. All results were statistically analyzed.Results:VEGF expression was found in 20 cases (71.4%) of HCC, 17 (85%) of HCV-related cirrhosis, 11 (55%) of HCV-related chronic hepatitis and 2 (16.7%) of normal control group. There was significant inverse relationship between VEGF expression and grade of HCC. A statistically significant association between VEGF expression at one side and both intrahepatic metastasis and vascular invasion in the other side in HCC group was found (P value was < 0.05 and < 0.01 respectively). VEGF expression was significantly higher in HCC-associated cirrhosis and chronic hepatitis than that of the tumor (P value <0.005), and significantly higher in HCV-related cirrhosis than HCV-related chronic hepatitis group (P value < 0.005). There was a significant association between VEGF expression and grade of inflammation and stage of fibrosis (P value < 0.01). Conclusions:VEGF plays a crucial role in the pathogenesis of HCV-related HCC as well as in the angiogenesis of HCV related chronic liver disease.