In conclusion, we identified five hub genes (CRYBB1, RIMBP3C, CEACAM4, HAMP, and LYL1) referred to both sunitinib and immune infiltration in ccRCC based on GSE65615, GTEx, and TCGA datasets and further validations refined CRYBB1, CEACAM4, and HAMP which presented a crucial role in the development and progression of ccRCC and implicated in sunitinib resistance and immune infiltrations in ccRCC, which could lead to a better insight into the tumorigenesis and development of ccRCC and the ccRCC‐special TME. The gene discussed is CRYBB1; the disease is nonpapillary renal cell carcinoma.