Abstract: Hypoxia induced factor-1α(HIF-1α)is a key regulation factor that helps tumor adapt itself to the hypoxia microenvironment. It regulates the expression of more than 100 target genes that control cell proliferation and survival, metabolism, angiogenesis, invasion and metastasis. HIF-1α/p300, a core complex that regulates downstream genes expression, is considered as a potential antitumor target. This review summarizes HIF-1α signal pathway, the binding mode of HIF-1α/p300 protein-protein interaction and recent development on the HIF-1α/p300 protein-protein interaction inhibitors, which provides reference to the design of this kind of inhibitors.