 The hypoxia-inducible factor 1, HIF-1, is a crucial survival pathway for tumor cells that has been recognized as an important cancer drug target due to its strong correlation with tumor metastasis, angiogenesis, poor patient prognosis, and resistance therapy. Recent advances in cancer biology have highlighted the HIF-1-alpha pathway as a promising target for novel strategies of cancer therapy, despite challenges in targeting this pathway. This review summarizes the role and regulation of the HIF-1-alpha in cancer and recent therapeutic approaches targeting this important pathway. This article was authored by Georgina and Masoud and Weili.