Youth-onset non-small cell lung cancer (NSCLC) is a heterogeneous disease. It has a unique clinicopathology and special genetic background. In this study, three key genes, CDC20, CCNB2, and BUB1, have been identified in youth-onset NSCLC tumor tissues based on the TCGA and GEO cohorts. Functional enrichment analysis reveals that the “oocyte meiosis,” “cell cycle,” and the “P53 signaling pathway” are significantly enriched. Additionally, four survival genes, including AKAP12, CRIM1, FEN1, and SLC7A11, that affect the prognosis of youth-onset NSCLC patients are identified in this study. Finally, we construct a risk model to predict the overall survival of youth-onset NSCLC patients, the AUC of the risk model in 1, 3, and 5 years of overall survival is 0.808, 0.844, and 0.728. This study aims to provide a novel idea to explore the pathogenic genes of youth-onset NSCLC.