Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation in which the failure of chondrocytes to maintain a homeostatic balance between matrix synthesis and degradation plays pivotal role. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. Yunke (Tc-99-MDP) has been widely used in China for the treatment of OA with good efficacy in suppressing inflammation. But the effect target and the underlying molecular mechanism in chondrocytes is still largely unknown. In this study, we examined the anti-inflammatory effects of YunKe in IL-1 beta-induced inflammatory chondrocytes HC-a cell lines and found KLF4 enhanced significantly in Yunke treated inflammatory cells. Lentivirus-mediated KLF4 knockdown or overexpression models were employed to detect the role of KLF4 in IL-1 beta-induced HC-a cells. Real-time RT-PCR and western blot were used to measure the expression of classic inflammation indicator MCP-1, IL-6, apoptosis regulators caspase-3, Bcl-2 and key factors of signal pathways. It was found that without KLF4, the anti-inflammation effect of Yunke will declined obviously and induced cell apoptosis, meanwhile, over-expression of KLF4 raised the anti-inflammation effect of Yunke and reduced cell apoptosis further. Our results suggest that Yunke could ease the IL-1 beta-induced chondrocytes inflammation and reduced cell apoptosis via targeting KLF4 partly and NF-kappa B/iNOS/VCAM1 pathways played important roles in this biological course.