Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression ofANK3in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OSkirc databases. Genetic alterations ofANK3in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses ofANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation betweenANK3expression and immune infiltration in KIRC. We found thatANK3expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with lowANK3expression had poorer survival outcomes than those with highANK3expression.ANK3mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance.ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations ofANK3withPPARAandPPARGexpressions were confirmed. Expression ofANK3in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested thatANK3could serve as a prognostic biomarker and promising therapeutic target for KIRC.