Hypoxia, defined as reduced oxygen tension, is a common physiological phenomenon in both normal embryonic development and malignancy progression. Although severe hypoxia is generally toxic for both normal tissue and tumors, neoplastic cells gradually adapt to prolonged hypoxia though additional genetic and genomic changes with a net result that hypoxia promotes tumor progression and therapeutic resistance. Hypoxia promotes cancer progression by regulating various aspects of cancer biology, including radiotherapy resistance, metabolism, angiogenesis and invasion/migration.