Angiogenesis is the process of formation of new blood vessels. It is of vital importance during the development and progression of solid tumors. Forty-six individuals were the subjects of this study; 12 patients with chronic hepatitis C, 12 patients with liver cirrhosis, 12 patients with HCC and 10 healthy subjects. Blood levels and hepatic expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and urokinase plasminogen activator (u-PA) were assessed in these patients to clarify their value as early predictive markers for malignant transformation. VEGF serum level was low in patients with liver cirrhosis compared to patients with chronic hepatitis C while its hepatic expression was comparable in both groups. In contrast, HGF and u-PA serum levels and degree of hepatic expression were significantly elevated in cirrhotics compared to patients with chronic hepatitis C. Patients with HCC had marked elevation of VEGF, HGF and u-PA circulating levels and higher degree of hepatic expression compared to other groups. A positive correlation was detected between hepatic expression of VEGF, HGF and u-PA in different groups studied. A similar positive correlation was also noticed between the circulating levels of these angiogenic mediators in patients with HCC. Likewise, a positive correlation was noted between serum levels of VEGF, HGF and u-PA and the degree of hepatic immunoreactivity of the same factors in patients with HCC. Conclusion: VEGF, HGF and u-PA have direct relationship with angiogensis in HCC and can be used as satisfactory markers for early diagnosis of HCC. VEGF, HGF and u-PA play an important role in fibrinolytic system activation and in the pathogenesis of liver fibrosis.