Herein, we found that penfluridol transcriptionally inhibited OCT4 and Nanog expressions and enhanced the response to a TKI, sunitinib, in various ccRCC cells, but the role of CXCR4 in the anti-CSC activity of penfluridol needs to be further investigated. Here, POU5F1 is linked to nonpapillary renal cell carcinoma.