Abstract: Objective To evaluate the clinical value of tissue polypeptide antigen(TPA) combined with ProGRP, CEA, NSE, SCC and CYFRA21-1 on patients with lung cancer. Methods TPA, ProGRP, NSE, CEA, CYFRA21-1 and SCC in the serum of 238 lung cancer patients, 25 benign lung diseases patients and 65 healthy controls were determined by chemilumineseent immunoassay(CLIA) and electrochemilumineseent immunoassay(ECLIA). And 33 cases of patients with lung cancer were followed up. SPSS19.0 statistical software and receiver operation characteristic(ROC) were applied to evaluate the clinical application value of tumor markers. Results The level of TPA was significantly higher in lung cancer groupmedian (130.45 U/L) than those in benign lung disease groupmedian (82.21 U/L) and healthy control groupmedian (70.96 U/L) (P=0.000, 0.002, respectively). ROC analysis showed the cut-off value to discriminate cancer from control was established at 130U/L for TPA sensitivity (50%), specificity (88.9%). The sensitivity of TPA was higher than other markers: ProGRP, NSE, CEA, SCC and CYFRA21-1, while the specificity was lower. With the rising of lung carcinoma staging, the levels of TPA as well as the positive rate were increased(P<0.05). Changes of TPA concentrations were correlated with tumor response. Elevated levels of TPA were found in the recurrent or metastasis disease patients, and the levels were decreased while the patients were sensitive to therapy. The sensitivity and effectiveness of the group of six tumor markers were the highest in all combined groups. Conclusion There is specifically clinical application value of these six tumor markers: TPA, ProGRP, NSE, CEA, CYFRA21-1 and SCC, for the diagnosis, curative effect, and prognosis monitoring of lung cancer.