Nuclear transcription factor one (HIF-1) plays an eminent role in the process ofcellular internal oxygen sensing system, increased levels of HIF-1 can increase the tumormetastasis therapeutic resistance and poor prognosis.In this study we discovered that oxacyododecindiona fungi-derived macro cyclic lactone have anti-tumor effects and allthese functions were achieved through specifically decrease the level of HIF-1α in multilevelwithout influencing HIF-2α.RT-PCR assay suggest that oxacyclododecindion can specificallydecrease the mRNA level of HIF-1 α increase the mRNA level of degradation relativeproteins including VHL, PHD3, P53, MDM2 □Westem blot suggest that oxacyclododecindiondistinctively decrease the synthesis of HIF-1 α mainly through the PI3K-AKTmTORand promote the degradation of HIF-lαthrough up regulate the protein level ofVHL ,PHD3.