Abstract: Objective To compare the efficacy and toxicities of pemetrexed or docetaxel as the salvage chemotherapy in patients with retreatment of advanced non-small cell lung cancer （NSCLC）after the failure of epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI）. Methods In this study，we retrospectively reviewed 120 cases with retreatment of advanced NSCLC patients in our hospital who were given pemetrexed （500mg／m2 d1）or docetaxel （75mg／m2 d1） as the salvage chemotherapy after the failure of EGFR-TKI. Twenty-one days was a cycle for the two regimens.Results The pemetrexed group was similar to the docetaxel group in objective response rate （13.4％ vs. 5.3％，P=0.307），the disease control rate （58.5％ vs.42.1％，P=0.093），the median progressionfree survival （2.83 months vs. 2.10 months，P=0.862），and the median overall survival （8.40 months vs. 9.10 months，P=0.527）. The median PFS was longer in the patients whose disease could be controlled by EGFR-TKI and who had performance status （PS）≤1（P＜0.05）. The pemetrexed group was lower than the docetaxel group in 1-4 degree neutropenia inhibition （41.5％ vs. 65.8％，P=0.013）. The non-hematology toxicities did not have significantly differences between the two groups （P＞0.05）. Conclusion A part of patients with retreatment of advanced NSCLC after the failure of EGFR-TKI may still benefit from pemetrexed or docetaxel as the salvage chemotherapy. The efficacy between the two groups does not have significantly difference. The patients whose disease can be controlled by EGFR-TKI or who have PS≤1 are more likely to benefit from the salvage chemotherapy. Most of the patients could accept the adverse reactions of the salvage chemotherapy.