A hypoxic microenvironment plays a critical role in the development and progression of tumors. The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their polarity and are converted to a mesenchymal phenotype, which is regarded as a critical event in morphogenetic changes during embryonic development, wound healing, and cancer metastasis. Recent advances in our understanding of the molecular pathways that govern the association of hypoxia with malignant tumors point to the epithelial to mesenchymal transition (EMT). The hypoxic microenvironment common to cancer cells emerges as an important factor in the induction of a pathological EMT, which is a key link in cancer progression. This review presents the potential molecular mechanisms underlying the hypoxia/HIF-dependent regulation of the EMT in cancer.