Pharmacological inhibition of Hpo/MST1/2 kinase activity inhibited p65/ZHX2 cooperativity, leading to diminished NF-κB target gene expression and inhibited ccRCC tumor growth, which can be alleviated by increasing the activity of ZHX2 or p65. This evidence concerns the gene NFKB1 and nonpapillary renal cell carcinoma.