The prognostic and predictive value of CA125 and CEA in patients with non-small cell lung cancer (NSCLC) is still uncertain.We retrospectively analyzed preoperative serum CA125 and CEA in 645 operable NSCLC patients and found elevated concentration of CA125 or CEA was associated with worse outcomes compared with normal expression.Moreover, CA 125 was an independent prognosis factor for operable NSCLC.[Background] The role of serum CA125 and CEA in the prognosis of non-small cell lung cancer (NSCLC) remains controversial,especially in early stage patients.The aim of this study is to analyze the prognostic value of CA125 and CEA in operable NSCLC.[Patients and Methods] We retrospectively analyzed 645 patients with NSCLC who underwent curative surgical resection for lung cancer at Zhejiang Cancer Hospital of China from 2006 to 2011.Micropartical enzyme immunoassay was used to measure preoperative serum CA125 and CEA.Univariate analysis and a mtdtivariable proportional hazard Cox regression model were applied to assess the prognostic significance of the different covariates.Kaplan-Meier was used to analyze survival curve.[Results] Both CA125 and CEA were correlated with stage,but also CA125 was different by grade,and CEA was related to histology.The Kaplan-Meier survival curves showed that patients with elevated CA125 or CEA had unfavorable disease progression-free and overall survival time compared to those with normal CA125 or CEA.Furthermore, multivariate Cox analysis revealed that elevated CA 125 had significantly higher risk for relapse (HR, 1.76;P=0.001) and death (HR, 1.80; P=0.000), while no significant differences were observed with elevated CEA for relapse (HR, 1.06; P=0.736) and death (HR, 1.25 ; P=0.119).[Conclusions] CA125 and CEA seem to play important role in disease progression and CA125 may be an independent predictive marker for prognosis in patients with NSCLC.