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Background and objective Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC). The studies are mainly focused on detection of EGFR gene for advanced NSCLC, and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown. This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC, and the relationship between the genotype and clinicopathologic features. Methods The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage I-IIIa NSCLC from Department of Pathology, Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit, and analyzed their correlation with clinical variables. Results The hotspot mutation rates in EGFR and KRAS were 34.5% and 13.1% respectively, and there were EGFR-KRAS double mutations in 3 samples. The mutation rate of EGFR was higher in females than that in males (39.5% vs 29.4%, P=0.076), significantly increased in adenocarcinomas (38.7%) compared to that in the other forms of NSCLC (P<0.01), but still lower than that reported in some Asian studies of advanced adenocarcinoma (-50%). Meanwhile, the mutation rate of KRAS was remarkably higher in males than that in females (16.6% vs 9%, P=0.048), increased in adenocarcinomas compared to that in the other forms of NSCLC, but the difference was not significant (P=0.268). Samples harbored EGFR mutation were younger than those harbored KRAS mutation (P=0.031,5), and had significant difference in gender between the two groups (P<0.01). Conclusion The mutation rate of EGFR in stag I-IIIa NSCLC patients was lower than that in advanced NSCLC patients. And the percentage of the NSCLC patients with EGFR-KRAS double mutations is 0.9%.