Osteoarthritis (OA) is the most prevalent disease of knee especially in the aged people. Isofraxidin (IF) is a coumarin compound refined from traditional Chinese medicines with potential anti-inflammatory ability. This study aimed to evaluate protective anti-inflammatory effects of IF in human OA chondrocytes. The chondrocytes were isolated from OA patients and pretreated with IF before treatment with IL-1β. The results showed that IF blocked IL-1β-stimulated production of NO and PGE2. In addition， IF inhibited the expression of COX-2， iNOs， MMP-1， MMP-3， MMP-13， ADAMTS-4 and ADAMTS-5， and increased the levels of aggrecan and collagen-II. Mechanistically， IF suppressed IL-1β-induced IκB-α degradation and NF-κB activation. In conclusion， our results demonstrate that IF inhibits inflammation in OA via the regulation of NF-κB signaling， and suggest that IF may be a potential therapeutic agent for OA.