Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide, displaying dismal prognosis. Growing evidence now links cuproptosis related genes (CRGs) and chromatin regulators (CRs) to cancer progression. However, the relationship between CRGs and CRs is not yet fully understood. Therefore, we aimed to reveal the connection and prognostic value of these two factors in LUAD patients. Methods: Cuproptosis related genes (CRGs) and chromatin regulators (CRs) were retrieved from previous top studies. For TCGA analysis, mRNA expression andclinical information for LUAD were downloaded via R package. Functional enrichment was analyzed through the ClusterProfler package. Cox regression analysis and LASSO regression analysis were utilized to train models for predicting outcome in LUAD. The Kaplan-Meier curve analyses was used to assess the prognosis for cases categorized as High-risk and Low-risk groups. DsigDB dataset was performed to screen the potential drugs for LUAD treatment. Results: We visualized an protein-protein interaction (PPI) network between CRGs and CRs. Functional analysis suggested that CRs were mainly enriched in chromatin modification and cell cycle pathways. The prognosis prediction model was successfully constructed and validated for the patients with LUAD. Moreover, we also showed 11-CRs-based model was an independent prognostic factor for LUAD patients. This CR-based model was associated with immune cells infiltration as well as immune checkpoint. Seven prospective drugs was detected for the treatment of LUAD patients. Conclusion: In conclusion, our findings provide unique information not available in previous studies, casting novel insights about the correlation between CRGs and CRs in LUAD. We also identified several prognostic biomarkers for the survival of patients with LUAD.