Abstract: Objective To test the levels of serum squamous cell carcinoma antigen(SCCA),neurone specific enolase(NSE),carcinomacmbryonic antigen(CEA) and cytokeratin-19 fragment(CYFRA21-1) in patients with lung cancer,and explore their role in the diagnosis and differential diagnosis of lung cancer. Methods The serum samples of 127 patients with pulmonary carcinoma,42 patients with pulmonary benign lesion and 100 healthy volunteers were prepared and tested by using ELISA for the levels of SCC,electro-chemiluminescence immunoassay for levels of NSE,CEA and CYFRA21-1.The sensitivity,specificity and accuracy of the single test and combined test in tumor markers were compared. Results The serum of SCC,NSE,CEA and CYFRA21-1 in patients with lung cancer were significantly higher than health volunteers and patients with benign lung disease(P<0.05).There were significant differences of the serum levels of SCC,NSE and CYFRA21-1 between lung cancer patients and benign lung disease patients(P<0.05).The level of SCC and CYFRA21-1 in patients with squamous cell carcinoma was significantly higher than patients with other subtypes.The level of NSE and CEA were highest in patients with small cell lung cancer and patients with glandular carcinoma,respectively.The sensitivity of combination test was 82.68%,and accuracy was 91.08%,significantly higher than that of each single sensitivity and accuracy. Conclusion SCC,NSE,CEA and CYFRA21-1 are helpful in the diagnosis of lung cancer.The combined detection can improve the sensitivity and accuracy.