Abstract: Objective To explore the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small cell lung cancer（NSCLC） previously treated with epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）. Methods In this retrospective study， 67 cases of NSCLC patients failed to EGFR-TKIs were enrolled. According to the treatment regimen， the patients were assigned to receive docetaxel（75 mg／m2 d1， n=31） or pemetrexed（500 mg／m2 d1， n=36） with 21 days for a cycle. The efficacy was evaluated according to response evaluation criteria in solid tumors（RECIST 1.1）. The toxicity was evaluated by international standard adverse reaction NCI CTC 3.0 version. The longterm survival was followed up and the Cox hazard regression model to analyze the influencing factors for the prognosis. Results All patients can be evaluated for the short-term efficacy. The response rates of pemetrexed group and docetaxel group were 19.4％ and 12.9％， and disease control rates were 58.3％ and 41.9％ without significant difference（P＞0.05）. In pemetrexed group， the incidence of grade 3-4 white blood cell reduction， thrombocytopenia， skin rash and elevated aminotransferase were all lower than that of docetaxel group（P＜0.05）. The median progression free survival（PFS） was 6.4 months in the pemetrexed group， higher than 4.7 months in docetaxel group with significant differences（P＜0.05）. No significant difference was observed in the median overall survival between both groups（P＞0.05）. Factors affecting the PFS included age， clinical stage， pathological type， PS score and save program. Conclusion Similar efficacy was observed between pemetrexed and docetaxel in NSCLC patients failed to EGFR-TKIs. However， the median PFS was relatively high， and the side effects were slight and could be tolerated in pemetrexed regiem. In view of the factors influencing the prognosis， it could be recommended to use in the treatment of the patients.