Objective: This study is to investigate the clinical efficacy of EGFR inhibitors on mutations in lung cancer patients with EGFR 19 and 21 exons. Methods: A total of 178 lung cancer patients were selected from January 2012 to September 2016 in this study and their EGFR mutations were analyzed by Real-time PCR. Then the patients were divided into Exon 19 group (n = 89) and Exon 21 group (n = 89) according to EGFR mutation status, and being treated with EGFR inhibitor erlotinib. Finally, the clinical efficacy and safety of the two groups were analyzed. Results: The average age of patients in Exon 19 group was lower than that of Exon21 group (P <0.05). The response Rate (RR) of the Exon19 group was 51.69%, while the RR of the Exon21 group was 48.31% (P> 0.05). The median overall survival (OS) were 56.00 months (95CI%: 54.054,57.946) and 49.00 months(95CI%: 47.682, 50.316)in the Exon 19 group and Exon21 group respectively. The median Progression-free Survival (PFS) were 50.00 (95CI%: 47.529,52.471) and 41.00 (95CI%: 38.738,43.262)in the Exon 19 group and Exon21 group respectively. Furthermore, the incidence of adverse reactions was similar between the two groups (P> 0.05). Conclusion: Lung cancer patients with EGFR 19 exon mutation are younger than those with EGFR 21 exon mutations, which may get more benefits from EGFR inhibitor therapy.