Abstract: Objective To investigate the value of serum carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), carbohydrate antigen 125(CA125)and neuro-specific enolase(NSE)in diagnosis of patients with lung cancer. Methods Totally 48 patients with diagnosed lung cancer and 40 patients with benign lung disease were selected and designed as lung cancer group and benign lung disease group respectively, and 35 healthy people with routine physical examination in outpatient department at the same time period were selected as healthy group. The serum levels of CEA, CA19-9, CA125 and NSE were compared among the three groups, and the sensitivity, specificity and accuracy of combined detection of CEA, CA19-9, CA125 and NSE in the diagnosis of lung cancer were analyzed. Results The serum levels of CEA, CA19-9, CA125 and NSE in the lung cancer group were significantly higher than those in the benign lung disease group and the healthy group(P<0.05). The levels of CEA, CA19-9, CA125 and NSE in patients in stage Ⅲ to Ⅳ of TNM were significantly higher than those in patients with stage Ⅰ to Ⅱ of TNM(P<0.05). The sensitivity and accuracy of combined detection of serum CEA, CA19-9, CA125 and NSE in the diagnosis of lung cancer were significantly higher than those of single detection(P<0.05), but there was no significant difference in specificity between the combined detection and single detection(P>0.05). Conclusion The sensitivity and accuracy of serum CEA, CA19-9, CA125 and NSE are high in the diagnosis of patients with lung cancer, which can provide reliable references for clinical screening and diagnosis.