Research has identified that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) possess large benefits for adenocarcinoma (ADC), although little benefit for squamous cell carcinoma (SCC). The aim of the present study was to investigate the percentage of patients with SCC with the EGFR mutations subset and the benefits of EGFR TKIs in SCC. In the present study, the EGFR mutations subset was detected with an amplification refractory mutation system in 1,359 clinical SCC tissues. The association of the EGFR mutations subset with clinicopathological parameters was evaluated using the Mann‑Whitney U test, and Kruskal‑Wallis H. Kaplan‑Meier survival analysis was used to estimate the effect of the EGFR mutations subset on SCC patient survival rates. A total of 94 out of 1,359 SCC patients were identified as having EGFR mutations, an EGFR mutation rate of 6.92%. The EGFR mutations subset in the 94 cases was identified as follows: 37.2% (35/94) in exon 19; 39.4% (37/94) in L858R; 5.3% (5/94) in T790M; 4.3% (4/94) in G719X; 2.1% (2/94) in L861Q; and 11.7% (11/94) in other mutations. Kaplan‑Meier survival analysis identified that the differentiation, pathological tumor, node, metastasis stage, lymph node metastasis and distant metastases were significantly associated with patients' survival (P>0.05; log‑rank test), and no significant difference was observed between TKI therapy and chemotherapy in terms of patient survival rates (P>0.05). In addition, the overall discordant rate of the EGFR mutations subset in SCC patients was relatively low. Due to the non‑significant difference between TKI therapy and chemotherapy in terms of patient survival and the lower discordance rate of the EGFR mutations subset in SCC patients, EGFR TKIs could be a recommended treatment for SCC.