Abstract：Objective To investigate the level of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21 1), 21-1 neuron specificity enolization beauty (NSE) and carbohydrate antigen 125 (CA125) in patients with lung cancer and its clinical value in differential diagnosis of lung cancer . Methods 52 patients with lung cancer, 40 cases of benign lung infections and 40 cases of healthy physical examination people were selected randomly and divided into the lung cancer group, control group and healthy group. The serum levels of CEA, CA125, NSE and CYFRA21-1 in three groups were detected by using electrochemical luminescence method. Results The levels of 4 kinds of serum tumor markers in lung cancer group were significantly higher than the control group and healthy group (P < 0.05). The sensitivity of single detection of CEA, CA125, NSE and CYFRA21-1 in the of lung cancer group were 44.23%, 38.46%, 42.31% and 44.23% respectively. The sensitivity of combined detection of four markers was 86.54%. The serum levels of CEA and CA125 in patients with adenocarcinoma were significantly higher than that of in small cell lung cancer and squamous cell carcinoma (P < 0.05). The serum CYFRA21-1 levels in patients with adenocarcinoma and squamous cell carcinoma were significantly higher than that of in small cell carcinoma (P < 0.05). The serum NSE level in patients with small cell carcinoma was in highest level. Conclusion The detection of four tumor markers has certain application value in the diagnosis of lung cancer, and the combined detection of these markers can significantly improve the sensitivity and accuracy of the diagnosis of lung cancer, so it is worthy for clinical popularization and application.