Objective To explore the application value of miR-493-5p, cholinesterase (CHE) combined with Golgiglycoprotein73 (GP73) detection in screening of liver cancer and disease assessment. Methods Ninety-eight patients with liver cancer (clinical stages: 31 cases in early stage, 35 cases in middle stage, and 32 cases in late stage) admitted to Anyang Fifth People's Hospital from July 2015 to July 2019 were selected as the observation group, and 104 patients who had healthy physical examination in this hospital during the same period were selected as the control group. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect miR-493-5, and the butyrylthio-choline method was used to determine the level of CHE, and the electrochemiluminescence method was used to determine the level of GP73. The expression levels of the three indicators in different groups were compared, and the predictive value of the three combined detection on the progression of patients with liver cancer were analyzed. Results The levels of miR-493-5p and CHE in the observation group were lower than those in the control group, and the level of GP73 was higher than that in the control group, the differences were statistically significant (P<0.05). The relative expression of miR-493-5p and the level of CHE were compared: early stage>mid stage>mid-late stage, the differences were statistically significant (P<0.05). The level of GP73 was compared: early stage<mid stage<late stage, the difference was statistically significant (P<0.05). The sensitivity, specificity and AUC of the combined detection of miR-493-5p, CHE, and GP73 were 92.10%, 94.50%, and 0.960, respectively, which were higher than those of single index detection, and the differences were statistically significant (P<0.05). Conclusion In clinic, the combined detection of miR-493-5p, CHE, and GP73 can be strengthened for the diagnosis of early liver cancer and the disease evaluation of patients.