Background and objective BIM gene is a member of the BCL-2 family, is involved in cell death. The aim of this study is to explore the relationship between BIM gene polymorphism and therapeutic efficacy in the retreatment advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitor (EGFR-TKI). Methods In the study, there were 123 patients who were diagnosed with advanced NSCLC in Zhejiang Province Cancer Hospital bewteen January 2009 to October 2012, all of who were received gefitinib and erlotinib therapy after failure to chemotherapy. We detected the genotype of peripheral blood leukocytes of patients with BIM gene polymorphism though polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 13.0. Results On the disease control rates, BIM gene with no polymorphism type was slightly better trend than polymorphism types in disease control rate DCR (75.5% vs 57.1%, χ2=2.931, P=0.087). Univariate analysis the median PFS, women were longer than men (6.9 months vs 4.5 months, χ2 =7.077, P=0.008). Non-smokers were longer than smokers (8.0 months vs 2.5 months, χ2 =15.277, P<0.001). Adenocarcinoma were longer than others pathological type (7.0 months vs 2.0 months, χ2 =14.978, P<0.001). The median PFS in BIM gene with no polymorphism type were longer than with polymorphism type (6.0 months vs 3.5 months, χ2=7.035, P=0.008). Multi-factor analysis showed that smoking, pathological type, the BIM gene polymorphism were the independent prognostic factors for PFS. Conclusion The patients with the BIM gene no polymorphism have longer the median progression-free time than the polymorphism types in retreatment advanced non-small cell lung cancer patients with tyrosine kinase inhibitor.