Abstract: Objective To investigate the clinical efficacy and adverse events of everolimus treated in patients with advanced nonsmall cell lung cancer （NSCLC） who underwent multi-line therapy. Methods Clinical data about 21 patients who underwent everolimus combined with targeted therapy or chemotherapy in our hospital from May 2013 to May 2014 were retrospectively analyzed to assess efficacy and toxicity. Results Of the 21 patients， 18 males and 3 females with median age of 52 years were in IV tumor staging. Four cases gave up for grade 2/3 adverse events， stable disease was found in 9 cases （52.9%） and progressive disease in 8 cases （47.1%）， resulting a disease control rate of 52.9%. The median progression-free survival was 3 months （95% CI: 2.337-3.663） and the median overall survival was 7.8 months （95% CI: 6.187-9.413）. The main grade 3/4 toxicity was stomatitis and interstitial pneumonia. Conclusion Everolimus combined with targeted therapy or chemotherapy in a way of gradually increasing the dose of everolimus shows good objective responses and well tolerance in advanced NSCLC patients undergoing multi-line treatment.