a-Feto protein (AFP) is the widely used tumor marker in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to assess the diagnostic and prognostic validity of a novel marker, serum Glypican-3 (GPC3) and to compare AFP in patients with HCC. One hundred and twenty-eight patients (75 patients with HCC, 55 patients with cirrhosis, and 28 healthy controls) were included in this study. Cut-off value of GPC3 was 3.9 pg/ml. AFP was divided into four subgroups, according to cut-off values with 13, 20, 100, and 200 ng/ml. Sensitivity, specificity, and positive and negative predictive values of GPC3 and AFP13, AFP20, AFP100, AFP200 subgroups and also GPC31AFP13, GPC3 1AFP20, GPC31AFP100, GPC31AFP200 combinations were compared. Serum GPC3 levels were significantly higher in patients with HCC and cirrhosis compared with control subjects (Po0.05). The median serum GPC3 levels were 3.9 pg/ml in controls, 5.51 pg/ml in patients with cirrhosis, and 5.13 pg/ml in those with HCC. The median serum AFP levels were 1.37 ng/ml in controls, 2.32 ng/ml in cirrhotics, and 50.65 ng/ml in HCC patients. The sensitivity, specificity, and positive and negative predictive values of GPC3 was 61.33, 41.82, 58.97, and 44.43%, respectively. The values for AFP were 68.57, 94.55, 94.12, and 70.27%, respectively. There was no correlation between GPC3 levels and prognostic parameters. GPC3 is not a useful diagnostic and prognostic marker for HCC.