〔Abstract〕 Objective To analyze the correlation between Ki-67 expression and EGFR mutations in lung adenocarcinoma and reveal their prognostic roles. Methods This study retrospectively screened lung adenocarcinoma patients who underwent surgical treatment between 2014 and 2020 in our department. Clinicopathological characteristics, Ki-67 expression and EGFR mutations were collected. The chi-square, Student's t-test and ANOVA were used for the comparison of Ki-67 expression and EGFR mutations among the groups. The Spearman's rho was adopted to evaluate the correlation between Ki-67 expression and EGFR mutations. Finally, the Log-rank test was used to reveal the prognostic roles of Ki-67 expression and EGFR mutations in lung adenocarcinoma. Results A total of 673 lung adenocarcinoma samples were enrolled in this study. The mean expression of Ki-67 was 21.37±20.43 [Median: 15(6～30)]. Among these subjects, 462 samples harbored EGFR mutations(68.65%). The expression of Ki-67 was much higher in males and smokers, and was positively correlated with tumor size and lymph node metastasis. The frequency of EGFR mutations was higher in females and non-smokers, and was negatively correlated with tumor size and lymph node metastasis. Samples with EGFR mutations had a lower Ki-67 expression level than those without EGFR mutations(18.82±17.75vs26.97±24.45,P<0.001). Consistently, the frequency of EGFR mutations in samples with a lower expression level of Ki-67 was significantly higher than that in patients with a higher Ki-67 expression(74.1%vs57.0%,P<0.001). The Spearman's rho analysis indicated that the rho was-0.129(P<0.001) between Ki-67 expression and EGFR mutations. Survival analysis suggested that a higher Ki-67 expression and EGFR wild type were significantly associated with a poorer prognosis of lung adenocarcinoma(P<0.05). The combined analysis of Ki-67 expression and EGFR mutations indicated that EGFR wild type patients with Ki-67>10 had a poorer prognosis than subjects with Ki-67 ≤10 and EGFR mutations. What's more, the HR value was 4.46(95%CI: 1.91～10.73,P<0.001). Conclusion Ki-67 expression was significantly negatively correlated with EGFR mutations in lung adenocarcinoma. Ki-67 expression and EGFR mutations might have a combined effect on the prognosis of lung adenocarcinoma.