Under the concept of "one airway, one disease", upper and lower airway inflammatory diseases usually coexist, and the whole airway can be regarded as one organ. The surface of upper and lower respiratory tract is covered with respiratory epithelium, which plays a vital role in immune monitoring and regulation. It is the first line of defense against various pathogenic microorganisms, allergens and tissue damage. In recent years, a large number of studies have suggested that epithelial-derived cytokines, such as interleukin (IL) -25, IL-33 and thymic stromal lymphopoietin (TSLP) are key regulators in the immune pathogenesis of allergic rhinitis, chronic rhinosinusitis and asthma. They are mainly involved in the inflammatory response of type 2 helper cells (TH), which are involved in linking innate and adaptive immunity. We reviewed the role of epithelial derived three cytokines in upper and lower respiratory tract diseases. Our review aims to provide new ideas for the clinical diagnosis and treatment of these diseases.