BACKGROUND: The expression characteristics of Keratin 18 (KRT18) in lung adenocarcinoma (LUAD) remain incompletely elucidated. This study aims to investigate the expression pattern of KRT18 in LUAD and its prognostic significance. METHODS: We analyzed the expression status of KRT18 in LUAD and its association with prognosis. Utilizing the UALCAN and STRING databases, we systematically evaluated the clinical phenotypic parameters of KRT18 and its protein-protein interaction network. Through enrichment analysis, we clarified its biological functions and associated signaling pathways, and simultaneously deciphered the association patterns between the tumor immune infiltration landscape and immune checkpoint molecules. RESULTS: High expression of KRT18 was associated with poor prognosis in LUAD patients and was closely correlated with tumor stage and pathological stage. Functional enrichment analysis revealed that KRT18 was significantly enriched in epithelial cell differentiation and intermediate filament pathways. Immune infiltration analysis showed that the expression of KRT18 was associated with tumor immune cell infiltration and immune checkpoints. Immunohistochemistry further confirmed the high expression of KRT18 in LUAD tissues. CONCLUSION: Therefore, KRT18 may serve as a biomarker for the prognosis and diagnosis of LUAD and also represents a potential target for immunotherapy.