Background: Endoglin (CD105) is a homodimeric membrane glycoprotein expressed on endothelial cells that can bind to transforming growth factor-â1 and transforming growth factor-â3. CD105 is only weakly expressed in normal tissues, but it is strongly expressed in tumor endothelia. Recent studies have suggested that CD105 is a proliferation-associated marker of endothelial cells. Aim of the work: This study tries to evaluate the role of serum endoglin as a non-invasive biomarker in diagnosis of liver cirrhosis and hepatocellular carcinoma. Subjects and Methods: AFP and endoglin were measured in 20 healthy control, 30 cirrhotic patients on top of HCV infection, 28 HCC patients on top of HCV infection and cirrhosis. Serum AFP was assayed by electro-chemiluminescence technique and serum endoglin was assayed by the quantitative sandwich ELISA technique. Results: Endoglin was highly significantly elevated in the HCC group (mean=8.63+2.38 ng/ml) than that of both the cirrhotic group (mean=7.17+2.28 ng/ml) and the control group (mean =6.1+1.49 ng/ml) , (P=0.035) and (p=0.001), respectively. AFP level was highly significantly elevated in the HCC group [median=121(56.75-219.75) ng/ml] than that of both the cirrhotic group [median=6.4(3.85-13) ng/ml)] and the control group [median=3.55(2.43-6.5) ng/ml)] (P=0.000) for both. The endoglin and AFP levels of the cirrhotic group were higher than that of the control group but this difference did not reach a statistical significant level (P=0.342) and (P=1.000), respectively. We found a positive significant correlation between endoglin and AFP for all studied subjects (r=0.412, p=0.000), and also there were direct significant correlation between endoglin and both tumour size and tumour number in HCC group [(r=0.587, p=0.001) and (r=0.421, p=0.026), respectively]. The sensitivity and specificity of endoglin of the HCC group over the non-HCC group were 39.3% and 82%, respectively, at a cut-off value of 9.1 ng/mL and AUC was 0.716, and that of AFP were 100% and 78%, respectively, at a cut-off value of 10ng/mL for AFP and AUC was 0.995. The sensitivity and specificity of both parameters together were 100% and 66%, respectively, at the same cut-off values. The Odds ratio of endoglin was 2.94 and 95% CI (1.035-8.396). The elevation of endoglin level in patients suffered from HCC than that in cirrhotic patients may be due to neoangiogensis accompanied to hypoxia associated to neoplastic tissue, or the development of an angiogenic response. Conclusion: Serum endoglin has the potential to be a novel complementary biomarker for assessment of the risk of the HCC development in the cirrhotic patients.