Objective To discuss the application value of PET/CT combined with serum levels of cancer embryo antigen (CEA),neuron specific enzyme (NSE), and cytokeratin 19 fragment 21-1 (CYFRA21-1) in the diagnosis of lung cancer. Methods 80 cases of patients with lung cancer and 69 cases of patients with lung benign disease were selected,and another 40 cases of healthy people carried out physical examination during the same period were selected.The accuracy of PET/CT combined with CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer was observed, and the receiver operating curve (ROC) was made to analyze the application value. Results The CEA, NSE and CYFRA21-1 levels in the lung cancer group were significantly higher than those in the lung benign disease group and the healthy group (P<0.05).The susceptibility of PET/ CT combined with CEA, NSE and CYFRA21-1 levels in the diagnosis of lung cancer was 87.62%, and the specificity was 92.38%,which were significantly higher than those by single detection method. Conclusion The susceptibility and specificity by the PET/ CT combined with CEA, NSE and CYFRA21-1 levels in the diagnosis of lung cancer are higher than those by single detection method,which has unique clinical value in the diagnosis of lung cancer.