Centromere protein W (CENP-W) is essential for chromosome segregation and mitotic assembly and has been recognized as a prognostic marker in several cancers. However, its significance in clear-cell renal cell carcinoma (ccRCC) remains underexplored. To investigate this, we analyzed transcriptomic data from the National Center for Biotechnology Information (NCBI) and The Cancer Genome Atlas (TCGA) to evaluate CENP-W expression and its associations with clinical outcomes, prognosis, and immune-related markers. Kaplan-Meier survival analysis indicated that elevated CENP-W levels are significantly associated with poorer overall survival in ccRCC patients. Further meta- and multivariate analyses confirmed CENP-W as an independent negative prognostic factor. Gene Set Enrichment Analysis (GSEA) revealed the involvement of CENP-W in immune-related pathways, notably PI3K-Akt and Wnt signaling. Pearson correlation analysis revealed strong associations between CENP-W expression and immune cell infiltration, cancer-associated fibroblasts (CAFs), CTLA4, and PDCD1. qRT-PCR assays confirmed elevated CENP-W levels in ccRCC samples. Additionally, GSEA and GO enrichment highlighted a relationship between CENP-W and lipid metabolism, with reduced CENP-W expression leading to a significant decrease in lipid droplet accumulation. This study identifies CENP-W as a potential biomarker and prognostic indicator in ccRCC, offering insights into personalized therapeutic strategies integrating tumor immunity to enhance the efficacy of immunotherapy.