Background <p>Recent research has increasingly highlighted the significance of various forms of cell death in contributing to tumor heterogeneity and modulating anti-tumor immunity. However, the potential implications of cuproptosis-related genes (CRGs) in lung adenocarcinoma (LUAD) remains poorly explored.</p> Methods <p>We conducted a comprehensive analysis of the expression profiles of 19 CRGs in LUAD based on The Cancer Genome Atlas (TCGA). Utilizing consensus clustering, we stratified the TCGA cohort into two distinct LUAD subtypes (Cluster 1 and Cluster 2). The expression of <i>CDKN2A</i> was further validated across multiple datasets, including TCGA, GEO, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA). The prognostic value of the <i>CDKN2A</i> was evaluated through univariate, multivariate, and survival analyses. Gene set enrichment analysis (GSEA) was performed to elucidate the molecular mechanisms associated with the <i>CDKN2A</i>. Additionally, we assessed the levels of immune cell infiltration in LUAD using the CIBERSORT, ESTIMATE, and XCELL algorithms.</p> Results <p>By systematically analyzing the genetic alterations of 19 CRGs in LUAD, we found 15 differentially expressed genes between LUAD and adjacent normal tissues. Subsequently, using the consensus clustering method, we classified LUAD patients into two molecular subtypes and cluster 2 had a poor prognosis. <i>CDKN2A</i> emerged as a key gene of interest, exhibiting elevated expression in LUAD and correlating with adverse patient outcomes. Moreover, immunoinfiltration analysis revealed differential levels of immune cell infiltration between the <i>CDKN2A</i> high and <i>CDKN2A</i> low expression groups.</p> Conclusions <p>Our findings indicate that <i>CDKN2A</i> may serve as an effective prognostic biomarker for LUAD and may offer valuable insights into potential immunotherapeutic strategies for these patients.</p> Clinical trial number <p>Not applicable.</p>