Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. Angiotensin-converting-enzyme inhibitors (ACEs) have a role in reducing malignant changes of the liver, and some of ACE inhibitors, such as captopril, inhibited angiogenesis and the growth of induced tumor. ACE inhibitor is associated with the suppression of the vascular endothelial growth factor (VEGF) at a clinically comparable dose, also markedly suppressed the hepato-carcinogenesis step. The present study aimed at evaluating the role of ACE inhibitors on the prognosis of HCC patients who have been treated by captopril. Measurements of liver functions, serum Alfa fetoprotein (AFP (and VEGF of 40 Egyptian patients with HCC (23 patients with Child-Pugh Band, 17 patients with Child-Pugh C) compared with 8 normal individuals at pre- and post-administration. There was statistically significant decrease of liver functions except serum albumin, serum AFP and VEGF in HCC patients at post administration compared with preadministration. In addition, at pre administration there was significant correlation of serum VEGF with albumin (r = - 0.379) and with serum AFP (r = 0.492) and at post administration with albumin (r = - 0.492) and with AFP concentration (r = 0.619). The prognostic value of serum AFP and VEGF was assessed by ROC curve showing an AUC of 0.689 and 0.907, respectively for identifying patients with HCC post administration of Captopril. In conclusions the results indicated that ACE inhibitor significantly inhibits tumor growth and angiogenesis along with suppression of the serum VEGF and AFP levels. This may be used in the clinical trials as anti angiogenic agents against cancer, and may be applicable as an anti-cancer agent providing a new strategy for cancer therapy.