Abstract: Objective To analyze the prognostic value of tumor markers CEA, CA125 and Cyfra21-1 in advanced non-small cell lung cancer(NSCLC) patients. Methods We retrospectively reviewed the clinical data of 120 NSCLC patients diagnosed in the Second Hospital of Yichang from June 2012 to May 2014, to observe the relationship between CEA, CA125, Cyfra21-1 levels and progression-free survival(PFS). Results Compared with squamous cell carcinoma, serum CEA levels in patients with adenocarcinoma was significantly increased (P<0.05); serum CA125 levels were significantly elevated in stageⅣadenocarcinoma patients(P<0.05); serum Cyfra 21-1 had no significant differences in general characteristics of patients (P>0.05). The PFS in patients with high levels of CEA, CA125 and Cyfra21-1 were 4.2, 4.5 and 4.3 months, with significant difference compared with healthy controls(P＜0.05). Conclusion The rise of CEA, CA125, Cyfra21-1 expression are significantly correlated with the progression-free survival of advanced NSCLC patients, and the clinicians can judge the prognosis by detecting the serum CEA, CA125, Cyfra 21-1 levels in patients.