Objective. This study was to examine the anti-inflammatory effect of sappanone A on interleukin- (IL-) 1β-stimulated osteoarthritis (OA) chondrocytes. Methods. Chondrocytes were pretreated with sappanone A for 2 h before subsequent IL-1β stimulation. The mRNA expression levels of iNOs, COX-2, aggrecan, and collagen-II were measured with qRT-PCR. The levels of TNF-α, IL-6, IL-8, MMP-3, and MMP-13 were determined by ELISA. The protein levels of iNOs, COX-2, ADAMTS-4, ADAMTS-5, aggrecan, collagen-II, p-p65, p65, IκBα, Nrf2, and HO-1 were assessed by Western blot. Results. Sappanone A inhibited the IL-1β-stimulated production of NO, PGE2, iNOS, COX-2, TNF-α, IL-6, and IL-8 in OA chondrocytes. In addition, sappanone A suppressed the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1β-stimulated OA chondrocytes. The degradation of ECM components was reversed by sappanone A. Sappanone A prevented NF-κB activation while enhanced Nrf2/HO-1 activation in IL-1β-treated chondrocytes. Conclusion. Sappanone A may be a potent therapeutic agent for OA.