Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. In this study, we evaluated the anti-inflammatory effects of Lico A on IL-1β-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that Lico A treatment significantly inhibited PGE2 and NO production induced by IL-1β. IL-1β-induced iNOS and COX-2 expression were also inhibited by Lico A. Lico A inhibited MMP1, MMP3, and MMP13 production in IL-1β-stimulated chondrocytes. Lico A also inhibited IL-1β-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, Lico A was found to upregulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of Lico A. In conclusion, our results suggested that Lico A showed anti-inflammatory effects in IL-1β-stimulated chondrocytes by activating Nrf2 signaling pathway.