Objective To investigate the joint clinical value of carcinoembryonic antigen (CEA), neuron-specific enolase degree (NSE), squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment (CYFRA21-1) in diagnosis of lung cancer patients. Methods 68 patients with lung cancer in this hospital from September 2012 to August 2013 were recruited , while 70 patients with benign lung disease and 90 healthy people as controls ,underwent automated immunoassay analyzer serological test.Two samples of serum CEA, NSE, SCC-Ag and content CYFRA21-1 were recorded to conduct comparative analysis. Results After testing, serum CEA in lung cancer group , NSE, SCC-Ag and CYFRA21-1 levels were significantly higher than those in the other two groups, the difference was statistically significant (P<0.05) between groups . The CEA level in adenocarcinoma was significantly higher than that in the other two types; NSE level in small cell lung cancer was significantly higher than that in the other two types; SCC-Ag and CYFRA21-1 levels in squamous cell carcinoma were significantly higher than those in the other two types , the differences were statistically significant (P＜0.05). High single detection specificity had no significant difference in the joint diagnosis, but the combined diagnostic sensitivity was 80.9 % and the accuracy was 83.3% , significantly higher than those in a single test, the difference was statistically significant (P<0.05 ). Conclusions The serum lung cancer patients carry CEA, NSE, SCC-Ag and CYFRA21-1 joint diagnosis could effectively improve the sensitivity and accuracy of disease diagnosis , with the exact value of clinical application.