In summary, the data show that IFI44 acts as an oncogene in ccRCC, promoting tumor progression through its interaction with PRDX1 while also shaping an immunosuppressive microenvironment, and suggest that IFI44 is a promising biomarker of prognosis and candidate therapeutic target for ccRCC. Here, PRDX1 is linked to nonpapillary renal cell carcinoma.