It has been demonstrated that virus infection is closely associated with development of many type of tumors, and a number of cellular signaling pathways are often deregulated by oncogenic virus after the invasion of host cells. Among them, deregulation of hypoxia signaling by oncogenic virus is particularly important and has been greatly concerned. In this paper, we mainly address how a variety of oncoproteins encoded by common human oncogenic virus tamper HIF signaling pathway, and how viruses respond in hypoxic microenvironment in term of tumor development, as well as summarize a model of oncogenic virus-mediated HIF signaling pathways and response to hypoxia stress, which shed a light on potential therapeutic targets and strategies against virus-associated cancers by interrupting hypoxia signaling.