Objective To detect the mutation rate of epidermal growth factor receptor (EGFR) in squamous carcinoma (SQC) of lung and to exam the relationship between p63 and survival of SQC patients with EGFR mutation. Methods SQC specimens were collected from the patients who received their initial treatment in our hospital between February 2010 and March 2013. The incidence of EGFR mutations was analyzed by automated direct sequencing, and immunohistochemical method was used to observe p63 expression. The patients were followed up and the impact of EGFR mutation and p63 expression upon survival of SQC patients was evaluated. Results Among the 262 histological diagnosed SQC patients, 16 (6.1%) had EGFR mutations, including exon 19 deletion (7 of 16 patients, 43.8%) and L858R point mutation in exon 21 (9 of 16, 56.2%), with no mutation of exon 18 and 20. SQC patients with EGFR mutations, compared with other SQC patients, had more females and non-smokers. The median overall survival (OS) time of 4 EGFR-mutated patients with p63 partial positive expression was 11.28 months (95% CI: 9.33-15.23 months), which was significantly longer than that of 11 EGFR-mutated patients with p63 positive expression (5.93 months [95% CI: 1.75-8.39 months], P=0.039). Conclusion EGFR mutation rate is 6.1% in our study, with all being exon 19 and 21 mutations. Patients presenting partial positive p63 expression have longer survival time than those presenting p63 positive expression.