Objective To evaluate the effect of different clinical features，tumor markers，TNM stage andtreatment strategies on pulmonary large cell neuroendocrine carcinoma（pLCNEC）. Methods A cohort of 149patients with pLCNEC were retrospectively enrolled. All data were collectedfrom the electronic medical records.The effect of clinical features and factors，including serum tumor markers（NSE，CA125，CA153，CYFRA21⁃1），TNM stage，pathological types（pure or combined），and treatment strategies on prognosis were analyzed by KaplanMeier curve and Cox model. Results Of the 149 patients，the median age was 63 years and 136（91.28%）weremales；100 were pure pLCNEC and 49 were combined pLCNEC. The median survival time was 18（10 ~ 32）months. The overall survival（OS）of patients with increased serum NSE，CA125，CA153 and CYFRA21⁃1 levelswas significantly shorter（HR = 2.959，4.249，5.198，1.84，P < 0.05）. The poor prognosis also associated withthese factors including tumor TNM stage（compared with stage I patients，the HR of stageⅢ and Ⅳ patients were4.074 and 9.470，respectively，P < 0.05），N and M（HR = 1.815，4.083，P < 0.05）. CA125，CA153，N and Mwere independent risk factors of poor prognosis. The stage Ⅰ ⁃ Ⅲ patients treated with surgery had significantlylonger OS than patients treated without surgery（HR = 0.357，P < 0.05）. The OS of combined pLCNEC patientswas similar to pure pLCNEC patients，but the OS of pLCNEC patients combined with small cell lung cancer wassignificantly shorter（HR = 2.051，P = 0.024）. Surgy⁃treatment was very efficient in patients with negative CEA，CA125 or CA153（HR = 0.256，0.479，0.388，all P < 0.05），but surgy⁃treatment became less efficient in patientswith positive CEA，CA125 or CA153（HR = 0.548，0.628，0.746，all P > 0.05）. Conclusion CA125，CA153，N and M are independent risk factors of poor prognosis of pLCNEC. The prognosis of pLCNEC combined with smallcell lung cancer is worse. Surgical treatment significantly improved the prognosis of stage Ⅰ⁃Ⅲ patients.