Hypoxia is a common feature of solid tumors.As transcripton factors,hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment;their target genes function in tumorigenesis and tumor development.Intriguingly,both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors.As downstream effectors of the mammalian Hippo pathway,YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB 1) complex,which restricts the transcriptional activity of YAP/TAZ.However,dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes,most of which are closely related to cancer.Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia,describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis,and highlight questions that might have a potential impact in the future.