Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and β4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and β4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and β4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes’ α5 and β4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes’ α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed β4. Psoriatic keratinocytes’ α5 was increased by IL-13/17A, decreased by IFN-γ; but β4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and β4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently