Abstract: Objective To evaluate the clinical value of combined detection of GPC3, GP73 and AFP in patients with HCC. Methods The study included 60 patients with HCC and 56 patients with liver cirrhosis. Fifty healthy volunteers served as control group. Sera of all cases were examined for GPC3 and GP73 by ELISA and correlated its levels with serum AFP level by MEIA. Results The serum expression and positive rates of GPC3, GP73 and AFP were significantly elevated in patients with HCC than those in cirrhotic patients and control group (P< 0.05). The levels of either GPC3 or GP73 were independent of the size of HCC, PVI, the AFP level and infection of HBV. The sensitivity of combined detection of AFP with GPC3 or GP73（73.33%, 80.00%）was better than that of AFP alone (53.33%). The combined detection of GPC3, GP73 and AFP maybe the best Youden index, the sensitivity and specificity being 86.77% and 86.02%, respectively. Either GPC3 or GP73 was detected in 42.86% of negative HCC for AFP. Conclusion It could be concluded that both GPC3 and GP73 can be considered as additional tumor markers to improve the diagnostic potential of AFP in HCC patients.