Abstract: Objective To explore the expression of serumgolgi protein 73 (GP73), glypican 3 (GPC3), alpha-fatoprotein (AFP), alpha-fetoprotein Lens culinaris agglutiin 3 (AFP-L3), carcinoembryonic antigen (CEA) in primary hepatocellular carcinoma (PHC) and their clinical significance. Methods Eighty-two patients with PHC and 60 patients with liver cirrhosis, 60 patients with chronic hepatitis and 40 healthy controls in Xiangya Hospital from May 2013 to June 2015 were enrolled in this study.The serumgP73 andgPC3 were detected by enzyme-linked immunosorbent assay, and the AFP-L3 was separated by micro column method.Determination of AFP and CEA were tested by electrochemical luminescence method.Logistic regression and ROC curve were adopted to evaluate the values of these indexes in the diagnosis of PHC. Results The levels of serumgP73, gPC3, AFP, AFP-L3 and CEA in primary liver cancer group were significantly higher than those in other three groups (P＜ 0.05), the levels of serumgP73, gPC3, AFP, CEA in liver cirrhosis group were significantly higher than those in chronic hepatitis group and control group (P＜ 0.05), and the levels of serumgP73, gPC3, AFP, AFP-L3 in chronic hepatitis group were significantly higher than those in control group (P＜ 0.05).SerumgP73 was positively correlated withgPC3, AFP, AFP-L3 in primary hepatic cancer group (r=0.563, P=0.000; r=0.527, P=0.008; r=0.542, P=0.000), and it was also positively correlated withgPC3 and AFP-L3 in liver cirrhosis group (r=0.602, P=0.000; r=0.517, P=0.004).ROC curve analysis showed that the AUC (0.838, 95% CI: 0.760 - 0.891) and diagnostic accuracy rate (84.7%) of AFP-L3 were the highest.Combination of serum tumor markers' AUC (0.884, 95% CI: 0.836 -0.947) and the diagnostic accuracy rate (89.6%) weregreater than the single detection.Multivariate Logistic regression analysis showed thatgPC3, AFP, gP73, AFP-L3 and CEA entered the regression model, and the model was: LogitP=2.63 + 0.025GP73 + 0.056GPC3 + 0.011AFP + 0.015AFP-L3 + 0.057CEA. Conclusion Serum tumor markers can be used as indicators for early diagnosis and differential diagnosis of PHC, and combined detection can significantly improve the accuracy of the diagnosis of PHC.