Although mutations and/or copy number abnormalities directly impacting the core Hippo kinases are relatively rare in human cancers, cancer cells manage to escape from Hippo regulation by means of other upstream and downstream Hippo regulators, including FAT1, SHANK2, SWI/SNF, Gq/11, VGLL4, etc. In this review, we focused on Hippo dysregulation in human cancers at the genomic level. The gene discussed is FAT1; the disease is cancer.