Objective: Lung adenocarcinoma (LUAD) is a common malignant tumor with a poor prognosis. The present study aimed to screen the key genes involved in LUAD development and prognosis. Methods: The transcriptome data for 515 LUAD and 347 normal samples were downloaded from The Cancer Genome Atlas and Genotype Tissue Expression databases. The weighted gene co-expression network and differentially expressed genes were used to identify the central regulatory genes for the development of LUAD. Univariate Cox, LASSO, and multivariate Cox regression analyses were utilized to identify prognosis-related genes. Results: The top 10 central regulatory genes of LUAD included IL6, PECAM1, CDH5, VWF, THBS1, CAV1, TEK, HGF, SPP1, and ENG. Genes that have an impact on survival included PECAM1, HGF, SPP1, and ENG. The favorable prognosis genes included KDF1, ZNF691, DNASE2B, and ELAPOR1, while unfavorable prognosis genes included RPL22, ENO1, PCSK9, SNX7, and LCE5A. The areas under the receiver operating characteristic curves of the risk score model in the training and testing datasets were .78 and .758, respectively. Conclusion: Bioinformatics methods were used to identify genes involved in the development and prognosis of LUAD, which will provide a basis for further research on the treatment and prognosis of LUAD.