Objective To evaluate the efficacy of chemotherapy for patients with EGFR (exon 19 and 21) mutation-negative non-small cell lung cancer (NSCLC).Methods One hundred and forty NSCLC patients with negative EGFR mutation (90 cases) or EGFR mutation (50 cases) underwent gemcitabine or vinorelbine plus cisplatin or carboplatin chemotherapy.Results In the EGFR mutation-negative patients,there were PR in 26 cases,SD in 48 cases,PD in 16 cases,the disease control rate was 82.2％.In the patients with EGFR mutation,there were PR in 14 cases,SD in 23 cases,PD in 13 cases,the disease control rate was 74.0％.The difference of disease control rates in the two groups was not significant (P =0.250).The progression free survival (PFS) of EGFR mutation-negative patients was 4.2 months (95％ CI 3.8-4.6) vs.4.0 months (95％ CI 3.6-4.4) in patients with EGFR mutation,with a significant difference (P =0.021).The overall survival (OS) of EGFR mutation-negative patients was 9.2 months (95％ CI 8.4-10.0) vs.7.8 months (95％CI,6.9-8.7) of patients with EGFR mutation (P =0.028).Condusions Chemotherapy can prolong the PFS and OS of EGFR mutation-negative patients.However,only the extension of OS has practical significance.