The Hippo pathway plays important roles in organ development,tissue regeneration,and human diseases,such as cancer.In the canonical Hippo pathway,the MST1/2-LATS1/2 kinase cascade phosphorylates and inhibits transcription coactivators Yes-associated protein and transcription coactivator with PDZ-binding motif and thus regulates transcription of genes important for cell proliferation and apoptosis.However,recent studies have depicted a much more complicate picture of the Hippo pathway with many new components and regulatory stimuli involving both chemical and mechanical signals.Furthermore,accumulating evidence indicates that the Hippo pathway also plays important roles in the determination of cell fates,such as self-renewal and differentiation.Here,we review regulations of the Hippo pathway and its functions in stemness and differentiation emphasizing recent discoveries.