Objective: To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment. Methods: Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital. Results: The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men (P<0.001) and displayed a downward trend with age (P=0.03). The mutation rate of ethnic minorities was higher than Han (P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history (P<0.001), and patients without drinking history was higher than patients with drinking history (P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history (P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types (P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients (P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples (P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area (P<0.001). Multivariate analysis showed that gender (P<0.001), age (P=0.036), smoking history (P<0.001), pathological type (P<0.001), specimen type (P<0.001), and whether or not Xuanwei area (P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area (P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han (P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities (P=0.005). Conclusions: The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.