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Objective To discuss the role of ETS1 in development and progression of lung adenocarcinoma and to provide a theoretical basis for the screening of clinical biomarkers and targeted intervention for lung adenocarcinoma. Methods The UAlcan database was used to access the Cancer Genome Atlas (TCGA) database and the CPTAC database to compare the expression of ETSI in lung adenocarcinoma tissues and normal adjacent tissues. According to the expression of ETSI in lung adenocarcinoma tissues of the TCGA database, the overall survival (OS) of lung adenocarcinoma patients with high and low ETS1 expression was compared. Human lung adenocarcinoma A549 cells in the logarithmic growth phase were randomly divided into the si-NC group, si-ETS1 group, vector group and ETS1-OE group, which were transfected with si-NC, si-ETS1, peDNA3. 1 unloaded plasmid and peDNA3. 1-ETS1 overexpression plasmid by Lipofectamine™ 3000 transfection reagent, respectively. The relative expression of ETSI protein and mRNA was detected by Western blotting and real-time quantitative PCR, the cell proliferation ability (expressed by optical density value) was observed by CCK-8, the cell migration ability (expressed by scratch healing rate) was observed by cell scratch assay, and the cell invasion ability (expressed by the number of invasive cells) was observed by Transwell chamber assay. Results The results of TCGA and CPTAC database analysis showed that the expression of ETS1 in lung adenocarcinoma tissues was lower than that in the normal adjacent tissues (P<0.05). Compared with patients with low ETSI expression in lung adenocarcinoma, patients with high ETSI expression had longer OS (P<0.05). Compared with the si-NC group and the vector group, the relative expression levels of ETSI protein and mRNA in the si-ETS1 group decreased, and the relative expression levels of ETSI protein and mRNA in the ETS1-OE group increased (all P<0.05). Over the time of culture, the OD value of cells in each group showed an increasing trend. Compared with the si-NC group and the vector group at the same time point, the OD value of cells in the si-ETSI group increased, and the OD value of cells in the ETSI-OE group decreased (all P< 0.05). Compared with the si-NC group and the vector group at the same time point, the scratch healing rate and the number of invasive cells in the si-ETS1 group increased, and the scratch healing rate and the number of invasive cells in the ETS1-OE group decreased (all P<0.05). Conclusions ETSI expression in lung adenocarcinoma tissue decreases, which is associated with the prognosis of patients. The down-regulation of ETSI expression can accelerate the proliferation, migration and invasion of lung adenocarcinoma cells, suggesting its potential as a prognostic biomarker and therapeutic target gene for lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]