With the development of molecular pathology,many types of epidermal growth factor receptor (EGFR) mutations have been identified.The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations,especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations),has not been fully understood.This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations.Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital,Wuhan,were retrospectively reviewed.The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed.Among these patients,377 patients had only the EGFR del-19 mutation,362 patients the EGFR L858R mutation in exon 21,33 patients single rare mutations and 37 patients complex mutations.Among these 809 patients,239 patients were treated with EGFR-TKIs.In all the 239 patients,the disease control rate (DCR) was 93.7％ with two patients (0.2％) achieving complete response (CR),the median progression free survival (PFS) was 13.0 months (95％ confidence interval [CI],11.6-14.4 months),and the median overall survival (OS) was 55.0 months (95％ CI,26.3-83.7 months).Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P＜0.001).Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P＜0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations).Furthermore,the patients with single rare mutations had shorter median OS than in those with other mutations.Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308,95％ CI,0.191-0.494,P＜0.001) and OS (HR=0.221,95％ CI,0.101-0.480,P＜0.001).The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations.The prognosis of the single rare EGFR mutations is depressing.EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR.Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.