Abstract: Objective To evaluate the effect and cost-efficacy of the second-line treatment of advanced non-small cell lung cancer（NSCLC）by regimens of docetaxel， pemetrexed，erlotinib and gefitinb. Methods A total of 160 patients with advanced NSCLC were assigned to docetaxel，pemetrexed，erlotinib and gefitinb groups（40 cases in each group）. The dosages of the 4 drugs were docetaxel 75mg／m2 dl，pemetrexed 500mg／m2 dl，erlotinib 150 mg/d and gefitinb 250mg／d. The former two regimens were given 2.6 cycles（21 days as a cycle）. The later two regimens were given till the disease progressed or intolerant side effect emerged. The effective rate，disease control rate，progress-free survival（PFS） and cost-efficacy ratio were analyzed. Results The effective rate of docetaxel，pemetrexed，erlotinib and gefitinb group was 7.5％，10.0％，20.0％ and 22.5％（P=0.165）；disease control rate was 32.5％，50.0％，65.0％ and 52.5％（P=0.035）；median PFS was 2.7，2.8，3.5 and 3.5months （P=0.677）；the cost of per unit （1 month）increasing of PFS was 5635.6，10 279.6，20 814.0 and 17 587.8 yuan. Taking docetaxel group as control，the cost-efficacy ratio of pemetrexed，erlotinib and gefitinb group was 46 434.7，119 729.4 and 103 171.0 yuan／month. The sensitivity analysis supported the results of benefit-cost evaluation. Conclusion Docetaxel，pemetrexed，erlotinib and gefitinb have no statistically significance in the second-line treatment of advanced NSCLC. Docetaxel had better cost-efficacy. Erlotinib and gefitinb have less side effects but the most expensive cost.