Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who have an EGFR mutation. However, little has been reported about the association between EGFR exon 19 deletions or an exon 21 mutation (specifically the L858R point mutation) and survival rates following first-line EGFR-TKI treatment in patients with NSCLC. As a retrospective study, 72 patients with stage IIIB/IV NSCLC carrying EGFR mutations (exon 19 deletions or an exon 21 mutation) were enrolled between 1 January 2008 and 31 December 2013, and all of the patients received first-line EGFR-TKI treatment. The associations between EGFR mutation status or clinical characteristics and response rate (ORR), progression-free survival (PFS) or overall survival (OS) were analyzed. Patients with exon 19 deletions (37 cases) had a higher ORR (75.7 vs. 51.4%; P=0.032), disease control rate (DCR; 89.2 vs. 68.6%; P=0.031), modified median PFS (13.2 vs. 10.8 months; P=0.030) and OS (30.2 vs. 25.6 months; P=0.030) compared with those with an exon 21 mutation (35 cases). Cox multivariate analysis indicated that sex, histological type and smoking history were key factors that affected PFS and OS. Mutations status was associated with PFS, but not OS. Following EGFR-TKI therapy, a better ORR, DCR, PFS and OS was observed in patients with EGFR deletions in exon 19 compared with those with an exon 21 mutation. The EGFR mutation status of patients with non-small cell lung cancer may therefore predict the efficacy and prognosis of EGFR-TKI.