Hypoxia and HIF-1 are major factors which play essential roles in cancer cell adaptation to pathophysiological restrictions like poor vasculature and limited metabolic supplies caused by hypoxic tumor core. Transcription factor Yin-Yang 1 (YY1) has been linked with cell proliferation, cell cycle progression and deregulation; it exerts oncogenic effects contributing to cancer progression. YY1 and hypoxia/HIF1 independently share several common aspects of malignant transformation. In this review, we discuss the oncogenic roles of YY1 and hypoxia/HIF1 and sum up the possibilities indicating their association in cancers. We advocate the idea that simultaneously modulating the effects of hypoxia and YY1 might provide a better approach and targeting strategy while treating solid cancers.