Abstract: On the concept of ‘united airway diseases’, the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The airway plays a vital role in immune surveillance and modulation as the firstline of defense to various infective pathogens, allergens and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Here, we review the role and association of these three epigenetic cytokines in respiratory diseases, with a view to further understand the mechanism of the united airway diseases.