Cytokines are some of low molecular weight proteins that serve as chemical messengers in the innate and adaptive immune systems of . Defender against cell death 1 (DAD1) is likely to be involved in programmed cell death, which is an integral part of growth and development in multi-cellular organisms and is involved in response to a range of internal and external stimuli. Allograft inflammatory factor-1 (AIF-1) is a binding protein. AIF-1 plays an important role in the survival and pro- inflammatory activity of macrophages and disintegrin. This paper reviews the advance in the research of functions and structures of DAD1 and AIF-1 and current research progress of the two cytokines in fish. We the outlook with regard to innate immunity of fish and new direction in the future research of fish AIF-1 and DAD1.