We find that, in addition to inhibiting hypoxia-inducible factor 2α, a major oncogenic driver in Von Hippel-Lindau−/− ccRCC, YAP also blocks nuclear factor κB (NF-κB) signaling in ccRCC to inhibit cancer cell growth under conditions where hypoxia-inducible factor 2α is dispensable. This evidence concerns the gene YAP1 and cancer.