Five groups were assigned to include intrahepatic cholangiocarcinoma ( ICC, n=30 ) , liver cirrhosis (LC,n=30),metastatic carcinoma (MCA,n=30) and 30 healthy subjects.The serum level of GPC3 was measured by a sandwich method of enzyme-linked immunosorbent assay ( ELISA ) and alpha-fetoprotein (AFP) by microparticle enzyme immunoassay (MEIA).The serum levels of GPC3 and AFP were significantly higher than those of other groups (P<0.05).At a cut-off value of 3.5μg/L,the sensitivity and specificity of GPC3 in the diagnosis of HCC was 83.3%and 76.7%respectively.The sensitivity of combined measurement of GPC3 and AFP was better than GPC3 or AFP alone.Detectable GPC3 was significantly correlated with the presence of viral hepatitis markers and tumor size.However there was no obvious difference in tumor thrombi in portal vein ( PVTT), tumor number, age, gender or hepatic function of HCC.Thus,as a sensitive serum diagnostic marker for HCC ,GPC3 may be a good supplement to AFP in differentiating HCC from non-malignant chronic liver diseases and other liver cancers.