Abstract: Objective To explore the value of combined detection of serum carcinoembryonic antigen(CEA), alpha fetoprotein(AFP), carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)in diagnosing primary liver cancer. Methods A total of 41 patients with primary liver cancer were selected as liver cancer group, the 39 patients with benign liver disease were selected as benign group, and 40 healthy people with physical examination were selected as control group. The serum CEA, AFP, CA125 and CA199 levels and positive rates were compared among the three groups, and the sensitivity, specificity and accuracy of combined detection of the four indicators in the diagnosis of primary liver cancer were calculated. Results The serum levels of CEA, AFP, CA125 and CA199 in the liver cancer group were significantly higher than those in the benign group and the control group(P<0.05). The positive rates of CEA, AFP, CA125, CA199 and their combined detection in the liver cancer group were significantly higher than those in the benign group and the control group(P<0.05). The sensitivity and accuracy of combined detection of serum CEA, AFP, CA125 and CA199 were significantly higher than the results of single detection of each index(P<0.05). The specificity of combined detection was 89.87%, which showed no significant difference compared with single detection of each index(P>0.05). Conclusion The combined detection of serum CEA, AFP, CA125 and CA199 is of great value in the diagnosis of primary liver cancer, which can improve the detection efficiency.