Hepatocellular carcinoma, is one of the most common malignancies in the world, it is a multifocal and aggressive tumor and it is the fourth most common tumor in the world today. It is now a rather common malignancy in Egypt. HCC is one of the major causes of death because of its high frequency and poor prognosis, it is responsible for about one million deaths annually with only few patients surviving beyond one year. It is one of the few human cancers for which an etiological factor can be identified in most cases. The two main etiological factors for hepotocellular carcinoma are cirrhosis and viral hepatitis (HCV and HBV), also the risk of HCC increased with prolonged dietary consumption of aflatoxins, alcohol or iron overload. In Egypt the incidence of HCC is increased due to the high prevalence rate of HCV which accounts for most of cirrhosis and HCC cases. Early detection of patients with HCC is attractive because it gives better prognosis, and early detection is not difficult if tumor markers and medical imaging were possible, so the need for easy reliable tumor marker is mandatory because AFP may be within normal in HCC cases, and if elevated it needs high cutoff values to be sure of the diagnosis also imaging is important to be combined with the tumor markers to be sure of the diagnosis, so 3D US used with 2D US to be more accurate, and it can measure the actual volume of the tumor and any local spread. The aim of this study was to determine the value of SACE and Angiotensin II as well as CA 19-9 as possible tumor markers of HCC developing on top of liver cirrhosis. The study was conducted on 40 HCC cases, 40 LC cases and 25 normal subjects. We determined the levels of AFP, CA 19-9, SACE and Ang. II for all cases together with liver biochemical profile, viral marker, abdominal US (2D US and 3D US) and histopathologic examination of the hepatic focal lesion in HCC cases. We concluded that the diagnostic sensitivity of AFP at a cutoff 200 ng/ml was17.5% and the specificity 100%. At a cutoff value of 31ng/ml CA 19-19 showed a sensitivity of 97.5% and a specificity of 90%. Serum ACE was 90% sensitive and 82.5% specific at a cutoff 70 U/L while Ang. II was 100% sensitive and 95% specific at 48 pg/ml. Serum ACE showed significant negative correlation with the tumor volume measured by 3D US (r = -0.497, p < 0.05).