The mucosa-associated lymphoid tissue is the first line of defense against pathogens in fish. In recent years, the nasal-associated lymphoid tissue (NALT) of fish has attracted worldwide attention from researchers, and has proved to be an important site for antigen recognition and initiation of mucosal immune response in olfactory organs. NALT exerts a rapid local immune response following bacterial, viral and parasitic infections. Intranasal inoculation of fish targeting NALT can provide excellent immune protection. However, the complex network of cells and molecules in NALT and their interaction mechanisms are still largely unknown. Here, the latest progress in studies on the structure and function of olfactory organs, cellular and molecular networks and immune response of NALT, as well as response to intranasal inoculation and its immunoprotective effect on fish are reviewed. This information will promote understanding of the immune defense mechanism exerted by fish NALT locally in the mucosa, which will benefit the design and development of novel mucosal vaccines.