In vitro, we observed that penfluridol treatment suppressed GLI1 expression in ccRCC cells harboring WT or mutant VHL. The GLI1-specific inhibitor, GANT58, can further enhance the penfluridol-induced inhibition of proliferation, OCT4 and Nanog mRNA expressions, and induction of apoptosis. Here, VHL is linked to nonpapillary renal cell carcinoma.