Inflammatory injury is a key pathological factor for many clinical diseases, which can often cause serious complications or death. However, traditional clinical methods are rare and with limited therapeutic effects. Recent studies show that tumor necrosis factor alpha stimulated gene inducible protein 6 (TSG-6) can participate in many inflammatory processes through its association with different ligands in vivo, and play an important role in anti-inflammatory and promoting extracellular matrix remodeling. In this review, we focus mainly on the basic biological characteristics and mechanism of TSG-6, and summarize its anti-inflammatory effects in pathologic scars, neuroinflammation, atherosclerosis and joint inflammation.