HCV infection patients without any complications, group III: 100 HCV infected patients complicated with cirrhosis and group IV: 150 HCV infected patients complicated with (90 localized and 60 metastatic) HCC. Detection of serum GPC3 and alpha-fetoprotein using an enzyme-linked immunosorbent assay (ELISA) were done to all subjects. Results: When analysis of variance was done between the four groups, a highly statistical significant difference was found between these groups regarding the mean serum levels ofAFP and GPC-3 where the highest increase of three markers were found in the HCC group. The combinedAFP and Glypican- 3 improve the sensitivity and specificity ofAFP alone. Conclusions: GPC- 3 could be a sensitive, specific and accurate marker for early detection of HCC diagnosis.