The innate immune system is the first line of defense against viral infection. Upon virus infection, host cells trigger immune response and initiate the immune mechanism of inhibiting virus replication. Meanwhile, viruses have evolved various mechanisms to counteract the host innate immune signaling pathway, including evading from host pathogen recognition receptors recognition and hijack host proteins to facilitate their own proliferation. DEAD (Asp-Glu-Ala-Asp, DexD/H) helicase family is a class of functional proteins existing in host cells. They play a key role in various cellular processes, such as transcription, splicing, mRNA synthesis and translation. Members of this family have the ability to recognize RNA and participate in multiple cellular processes, so they can affect the innate immune responses caused by viral infection in many ways. This paper reviews the research on DEAD-box RNA helicase in innate immunity to provide reference for related studies.