This study examined the prognostic role of CENPW in clear cell renal cell carcinoma (ccRCC) using publicly available data from The Cancer Genome Atlas (TCGA). In order to clarify the relationship between clinicopathological features and CENPW expression information obtained from the TCGA database, logistic regression analysis was applied. Moreover, the expression of CENPW was closely associated with multiple immune cell infiltrations, as determined by immune cell infiltration analysis. Kaplan-Meier survival analysis demonstrated that the lower the expression of CENPW, the better the prognosis (p < 0.001), indicating that CENPW is an important risk factor for patients with ccRCC. In addition, CENPW expression was also significantly associated with T stage (p < 0.001), N stage (p = 0.011), M stage (p = 0.001), Pathologic stage (p < 0.001) and Histologic stage (p < 0.001). It was found that CENPW could be an independent prognostic factor in both univariate and multivariate Cox regression analyses (p < 0.05). The results of GSEA analysis showed that CENPW was closely associated with several immune-related signaling pathways. Furthermore, in ccRCC, the expression of CENPW was closely associated with the infiltration of various immune cells and the expression of multiple immune cell gene markers. Finally, we verified the expression levels of CENPW using three different datasets from the Gene Expression Omnibus (GEO) database. The results of survival outcomes on GEPIA2 website were similar to the survival curves drawn based on TCGA database (all P < 0.05). In conclusion, we conclude that CENPW is a potential independent prognostic marker for ccRCC and plays an essential role in the tumor microenvironment by regulating immune cell infiltration.