Objective：To investigate the clinical efficacy of epidermal growth factor receptor（EGFR）mutated tyrosine kinase inhibitor（TKI）combination of pemetrexed and carboplatin versus chemotherapy alone after first-line EGFR-TKI resistance in advanced lung adenocarcinoma. Methods：Fifty patients with stage ⅢB~Ⅳ lung adenocarcinoma that had been treated with EGFR-TKI were divided into two groups：the combined group was treated with pemetrexed+carboplatin+gefitinib or icotinib. the other was chemotherapy alone. The therapeutic effect and side effects of the two groups were observed. Results：There was no significant difference in DCR and ORR between the combined group and chemotherapy group，and the mPFS of the two groups were 10.4 months vs 8.9 months（P > 0.05）；The mPFS of patients with T790M-negative were 11.1 months vs 8.3 months，and 7.6 months vs 5.7 months in patients with brain metastasis，which showed a better outcome in combined group（P < 0.05）；In the subgroups of smoking and different mutation types of EGFR，there was no significant difference in the curative efficacies between the two treatments. The main side effects of the two groups were myelosuppression、digestive tract reaction and fatigue. Skin rash and diarrhea in grade Ⅰ~Ⅱ were significantly higher in combined group（P < 0.05）. Conclusion：The combination treatment of continuation first-line EGFR-TKI plus pemetrexed and carboplatin in advanced lung adenocarcinoma has certain clinical promotion and application value.