Mucosal epithelium functions not only as a physical barrier, but also as a regulator of innate and adaptive immune responses against foreign substances and microorganisms. In particular, epithelial cells have been directly implicated in Th2 responses, serving as a critical interface between innate immune responses and Th2 immunity. Emerging studies have revealed the cellular and molecular mechanisms by which the epithelium modulates Th2 responses through the production of a group of epithelial-derived Th2-driving cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin. These epithelial-derived Th2-driving cytokines execute a regulatory function of the epithelium on mucosal immunity by promoting Th2 responses and maintaining the balance of host immune homeostasis and defense against various pathogens. Dysregulation of these Th2-driving cytokines can lead to detrimental Th2-dependent inflammatory responses, often manifested in various forms of allergic and inflammatory diseases.