Chicken Interferon-Alpha (IFN-α) is a type I interferon produced primarily by virus-infected cells and specialized immune cells in chickens (Gallus gallus), where it plays a central role in innate antiviral immunity. Upon binding to the avian type I interferon receptor complex (IFNAR1/IFNAR2), chicken IFN-α activates JAK/STAT signaling pathways, leading to induction of interferon-stimulated genes (ISGs) that inhibit viral replication, enhance antigen presentation, and promote activation of natural killer–like cells and adaptive immune responses. Chicken IFN-α is rapidly upregulated in response to economically significant viral infections such as avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and Marek’s disease virus (MDV), where it contributes to early antiviral defense but may also influence immunopathology if dysregulated. As a key mediator and biomarker of antiviral responses, IFN-α is widely studied in poultry immunology for vaccine development, genetic selection for disease resistance, and evaluation of antiviral strategies. In research settings, chickens serve as important animal models for avian influenza pathogenesis, viral oncogenesis (Marek’s disease), and developmental immunology, and characterization of chicken IFN-α enhances understanding of host–virus interactions, innate immune regulation, and interferon-driven antiviral mechanisms relevant to both veterinary health and comparative immunology.