Abstract: OBJECTIVE To analyze the pathogen distribution and serum XBIP and Caveolin-1 in advanced non-small cell lung cancer patients, so as to provide references for clinical diagnosis and treatment. METHODS A total of 170 cases of infected advanced non-small cell lung cancer patients in our hospital form Aug. 2011 to Dec. 2014 were enrolled in this study, and set as infection group. The genotypes and distribution of pathogens were identified by VITEK2 Compact automatic equipment. The serum XBIP, caveolin1, PTEN, PI3K and AKT proteins were detected by ELISA. Another 170 cases of healthy subjects and 170 cases of uninfected advanced non-small cell lung cancer patients at the same period in our hospital were taken as control group and uninfection group. RESULTS The pathogens isolated from the infected patients included 76 strains (44.7%) of gram-positive bacteria and 94 strains (55.3%) of gram-negative bacteria. The levels of serum XBIP, caveolin-1, TNFα, PI3K, PTEN and AKT proteins were increased significantly in infected advanced non-small cell lung cancer patients when compared with control group and uninfection group (P<0.05). CONCLUSION Advanced non-small cell lung cancer patients are easily suffered from pathogen infection, and the abnormal content of XBIP, caveolin-1, and PI3K/AKT/PTEN are involved in this process.