Squirrel Monkey (Saimiri spp.) Interferon-Beta (IFN-β) is a type I interferon produced by virus-infected epithelial cells, fibroblasts, macrophages, and dendritic cells, where it serves as a key early mediator of innate antiviral immunity. Closely related to human IFN-β at the structural and functional level, squirrel monkey IFN-β signals through the type I interferon receptor complex (IFNAR1/IFNAR2), activating JAK/STAT pathways and inducing interferon-stimulated genes (ISGs) that suppress viral replication, enhance antigen presentation, and promote natural killer (NK) cell and adaptive immune responses. IFN-β responses are central in squirrel monkey models of viral infections such as flaviviruses (including dengue and Zika virus), retroviruses, and other emerging pathogens, where the timing and magnitude of type I interferon induction influence viral control and immunopathology. Because squirrel monkeys are used in biomedical research for studies of neurotropic viruses, immune function, and vaccine evaluation, characterization of IFN-β is essential for understanding antiviral defense mechanisms, host–virus interactions, and cytokine-mediated inflammation. As both a biomarker and functional regulator of innate immunity, squirrel monkey IFN-β supports translational research bridging nonhuman primate models and human infectious and inflammatory disease biology.