Abstract: Objective To investigate the relationship between apolipoprotein A-I（ApoA-I） and clinicopathological features of patients with advanced non-small cell lung cancer（NSCLC）， as well as the effect of ApoA-I on the prognosis of advanced NSCLC. Methods Retrospective analysis was performed for 117 cases with histologically confirmed ⅢB and Ⅳ stage NSCLC patients in Changhai Hospital affiliated to Second Military Medical University from January 2009 to December 2014. All patients were classified into two groups based on the median value of baseline serum ApoA-I before treatment. The relationship between ApoA-I and clinicopathological features was studied. Univariate and multivariate analyses were performed to assess the prognostic effect of ApoA-I. Results All patients were divided into two groups： low serum ApoA-I levels before treatment（≤1.2 g／L， n=50） and high serum ApoA-I levels before treatment（＞1.2 g／L， n=67）. ApoA-I was correlated with greatest tumor diameter， clinical stage， serum Creactive protein before treatment， serum albumin and ECOG PS（P＜0.05）. The median overall survival（OS） of low and high ApoA-I levels patients were 10.1 months and 15.1 months with significant difference（P＜0.05）. Univariate analysis showed that the independent factors affecting the prognosis included smoking status， serum Creactive protein before treatment， serum albumin， clinical stage， N stage， ECOG PS and serum ApoAI level before treatment（P＜0.05）. Multivariate analysis by using Cox regression identified serum Creactive protein before treatment， clinical stage， ECOG PS and serum ApoA-I level before treatment as independent prognostic factors of all the patients. Conclusion A decreased serum ApoA-I level before treatment indicates poor prognosis in advanced NSCLC patients. ApoA-I could be a potential biological marker for advanced NSCLC patients.