A family of transcription factors, the interferon regulatory factors (IRF), was identified originally in the context of the regulation of the type I interferon (IFN)-alpha/beta system. The IRF family has now expanded to nine members, and gene-disruption studies have revealed the critical involvement of these members in multiple facets of host defense systems, such as innate and adaptive immune responses and tumor suppression. In the present review article, we aim at summarizing our current knowledge of the roles of IRF in host defense, with special emphasis on their involvement in the regulation of oncogenesis.