Abstract: Objective To explore the value of serum alpha-fetoprotein(AFP), golgi protein 73(GP73), α-L-fucosidase(AFU)and serum ferritin(SF)in the early diagnosis of primary liver cancer. Methods A total of 34 patients with primary liver cancer were selected as observation group, and a total of 35 patients with benign liver disease were selected as control group. The serum levels of AFP, GP73, AFU as well as SF and the condition of combined detection were compared between the two groups. Results The serum levels of AFP, GP73, AFU and SF in the observation group showed significant difference when compared with the control group(P<0.05). The serum levels of AFP, GP73, AFU and SF in the observation group in stages of Ⅲ to Ⅳ of TNM classification showed significant difference when compared with those in stages of Ⅰ to Ⅱ of TNM classification(P<0.05). The sensitivity and accuracy of serum AFP, GP73, AFU and SF in combination were 91.18% and 82.61%, respectively, which were higher than the single detection, and the differences were statistically significant(P<0.05). Conclusion The combined detection of serum AFP, GP73, AFU and SF can significantly improve the sensitivity and accuracy, which is of great value in the diagnosis of primary liver cancer.