Oxidative stress induced by harmful substances activates inflammatorysignaling pathways and causes excessive proliferation of keratinocytes,which is related to the occurrence of psoriasis. Rutin, a naturalcitrus flavonoid glycoside, exhibits protective effects againstoxidative stress. However, whether rutin is able to influence oxidativestress in keratinocytes remains unclear. In the present study, anin vitro cell model of human keratinocytes (HaCaT) treated withH2O2 was used to explorewhether rutin can prevent oxidative stress. The present findingssuggest that rutin protected HaCaT cells against oxidative damageby inhibiting ROS, NO and MDA secretion, increasing SOD activityand restoring GSH-Px activity. In addition, rutin supplement limitedIL-6, IL-1β and IL-23A production in HaCaT cells. Moreover, rutinupregulated Nrf2 expression, and promoted the downstream NQO1 andHO-1 expression. These results suggest that rutin may inhibit HaCaTcell oxidative stress by modulating the Nrf2-regulated pathway.