Objective Lung adenocarcinoma is one of the main types of lung cancer. This study was performed to examine the mechanism of lung adenocarcinoma, predict the key genes related to tumor development, and evaluate their prognostic significance in patients. Methods We downloaded the gene expression profile dataset (GSE18842, GSE74706, GSE101929) from the GEO database, the DAVID online database for GO and KEGG analysis of differential genes, the STRING database for screening candidate genes, Oncomine for the study of protein interactions, GEPIA, and other databases. The distribution and prognostic significance of the key genes were analyzed. Results The candidate genes were BUB1B, CDCA8, CDC20, BUB1, KIF20A, and AURKB. The results showed that the candidate genes were significantly higher in lung adenocarcinoma cells than normal cells. Conclusions These six candidate genes are highly likely to participate in the development of lung adenocarcinoma. As biomarkers of cancer, they are related to the poor prognosis of lung adenocarcinoma. These findings are anticipated to provide a reference for the study of lung cancer in future.