Therefore, in order to understand how M2 macrophages affect the prognosis of RCC, in this study, we used bioinformatics and in vitro experiments to explore the mechanism and screened nine M2 macrophage-related genes, including SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12, and a new prognostic model was developed for RCC based on the nine M2 macrophage-associated genes. This evidence concerns the gene LIPA and renal cell carcinoma.