Objective: To investigate the diagnostic value of serum GP73 combined with Dickkopf-1 and AFP in hepatocellular carcinoma. Methods: 117 cases of hepatocellular carcinoma in our hospital were collected as hepatocellular carcinoma group, 80 patients with hepatitis B virus as the hepatitis group, and randomly selected 80 healthy subjects as the control group from September 2014 to September 2016. The serums GP73, Dickkopf-1, AFP level of every group were detected by the enzyme-linked immunosorbent assay (ELISA), and the relationship between the GP73, Dickkopf-1, AFP between clinicopathological features were analyzed, the diagnostic value of GP73, Dickkopf-1 and AFP in hepatocellular carcinoma were analyzed. Results: The serums GP73, Dickkopf-1,AFP level of hepatocellular carcinoma group were higher than those of hepatitis group, control group, and the serum AFP level of hepatitis group was higher than that of control group, the difference was statistically significant (P<0.05). The GP73, Dickkopf-1, AFP in patients with classification B~C were higher than those in classification A among the Child Pugh classification, the difference was statistically significant (P<0.05). No statistical significance on difference of GP73, Dickkopf-1, AFP between different differentiation, tumor size, number of tumors was found (P>0.05). The sensitivity, specificity, positice predictive value, negative predictive value, and accuracy of GP73+Dickkopf-1+AFP in the diagnosis of hepatocellular carcinoma were higher than those of GP73, Dickkopf-1, AFP respectively, the difference was statistically significant (P<0.05). Conclusion: Serums GP73, Dickkopf-1, AFP in patients with hepatocellular carcinoma have high expression levels, combined with the three indicators can obviously improve the diagnostic value of hepatocellular carcinoma, which has clinically important reference value. [ABSTRACT FROM AUTHOR]