The invention relates to a novel anti-inflammatory drug, in particular to TLR4/MD2 inhibitors, i.e., compounds N-substituted-4-(5-dimethylamino-1-naphthalene)sulfonyl oxy benzoxazole-2-one and application thereof in anti-inflammatory drugs. The compounds provided by the invention can significantly inhibit the release of NO and inflammatory cytokines IL-1 beta and IL-6 of lipopolysaccharide (LPS) induced mouse macrophages, can remarkably inhibit the expression of TLR4, MYD88 and IRAK4 in a TLR4 inflammatory signaling pathway, and prevents NF-k kappa B from entering nucleus, thereby inhibiting the expression of inflammatory effector molecules COX2 and IL-6 and further exerting anti-inflammatory activity; the compounds can significantly inhibit xylene-induced ear swelling in mice, and has higher efficacy compared with the clinically commonly used anti-inflammatory drug-celecoxib at the same dose; the compounds can obviously inhibit the release of mouse lung tissue inflammatory cytokines induced by LPS; the compounds can significantly inhibit the joint swelling and expression of inflammatory factors thereof in rats with collagen-induced arthritis, and is better in curative effect compared with the clinically commonly used anti-arthritic drug-phenylbutazone; the maximum oral tolerance is 5000 mg/kg, and the compounds are basically non-toxic compounds.