Abstract: Renal cell carcinoma is a common type malignant tumor of the urinary system. The global incidence of renal cancer is 2. 2%. S100 proteins are involved in the regulations of proliferation, differentiation, apoptosis, and Ca²⁺ homeostasis, etc. S100 proteins are often closely associated with tumor progression. This review lists the expression changes of S100s and their functional significances in renal cancers, providing a new direction for the researches and treatments of renal cancer. The interpretation of S100 in the regulation of VHL/HIF signaling pathways should be a future direction.