The aim of this study was to observe the effect of NVP-AUY922, a next-generation HSP90 inhibitor, on the prevention of endotoxin-induced multiple organ failure in an animal model of endotoxemia, and to investigate whether it could inhibit the activation of the NF-κB signaling pathway, inhibit the release of pro-inflammatory cytokines, generate antioxidants, reduce apoptosis, activate autophagy, and reduce disseminated intravascular coagulation (DIC) to improve sepsis. Here, NFKB1 is linked to serum lipopolysaccharide activity.