Objective To study the base sequence mutations in exons 18-21 of epidermal growth factor receptor (EGFR) gene in the cancer tissues of patients with non-small-cell lung cancer ( NSCLC). Methods The specimens of cancer tissues from 72 NSCLC patients were preserved during the operation. Another 20 specimens of normal lung tissues were collected as the controls. The sequences of EGFR exons 18-21 in the cancer tissues and normal lung tissues were detected by direct sequencing. The EGFR mutations were analyzed. We compared the type of base mutation with NCBIs EGFR clinical gene mutation database ( ClinVar) to determine whether the sample mutation type was a pathological mutation and whether it corresponded to a specific drug response type. In addition, we analyzed the relationship between EGFR gene mutations and clinicopathological features of patients with NSCLC. Results The mutation rates of EGFR exons 18-21 in the NSCLC cancer tissues and normal tissues were 58.3% (42/72) and 0,respectively,with significant difference (P <0. 05). Mutations were found in all 4 exons. Sixty specific mutations were found in the detected exons of EGFR. The mutation types included point mutation,deletion mutation,insertion mutation,and insertion/deletion mutation. The mutation rates of exons 18-21 were 8.3% (6/72) , 29.2% (21/72) , 37.5% (27/72) , and 4.2% (3/72) , respectively. Each exon had specific mutation types. There were 4 , 21 , 9 and 1 point mutations in exons 18-21 , respectively. Other specific mutations included 13 insertion/deletion mutations in exon 19 , 2 deletion and 1 insertion/deletion mutations in exon 20 , and 1 insertion mutation in exon 21. There were 6 cancer-associated mutations in this study , including 1 benign variation ( c. 2361G > A) with mutation rate of 31. 9% (23/72),1 drug-sensitive mutation ( c. 2830T > G) with mutation rate of 2. 8% (2/ 72) , and 4 carcinogenic mutations. The overall rate of cancer-associated mutations was 12. 5% (9/72). The targeted drug-sensitive mutations got an overall rate of 2. 8% (2/72) . The mutation of c. 2573T > G in exon 21 caused Leu858Arg variation, which was a sensitive mutation in EGFR-targeted drug therapy. Conclusion There is a high mutation rate of EGFR exons 18-21 in NSCLC cancer tissues. The main mutation types are point mutation, deletion mutation, insertion mutation and insertion / deletion mutation. Exon 19 has the most mutations,and the mutations of exon 20 are the most complex. Of the 6 cancer-associated mutations,only one targeted drug-sensitive mutation is found in exon 21 . [ABSTRACT FROM AUTHOR]