Abstract: ObjectiveTo investigate the expression of plasma soluble podoplanin (sPDPN) in patients with non-small cell lung cancer (NSCLC) and its correlation with clinical stage and metastasis. MethodsA total of 218 patients with NSCLC treated at the Affiliated Suzhou Hospital of Nanjing Medical University from February 2021 to February 2023 were enrolled as lung cancer group. Additionally 100 healthy subjects undergoing physical examination during the same period were included as control group, and 1OO patients with benign lung diseases were enrolled as benign group. Plasma sPDPN, serum carcinoembryonic antigen（CEA), cytokeratin fragment (CYFRA211) levels were detected and compared among the three groups. Receiver operating characteristic （ROC) curve and Logistic regressionmodel wereusedtoanalyzethediagnosticefficacyof these serum markersfor NSCLCand identifythe risk factors of NSCLC development. The relationship between plasma sPDPN level and clinicopathological characteristics of NSCLC patients was also examined. Cox regression model was used to evaluate the prognostic impact of plasma sPDPN levels in NSCLC patients. ResultsThe levels of plasma sPDPN,serum CEA and CYFRA211 in lung cancer group were significantly increased （all P60years old,smok-ing,sPDPN,CEA and CYFRA211were independent risk factors for NSCLC(P