Hexamethylene diisocyanate was employed as a reactive additive to capture lithium polysulfides formed at the cathode of lithium-sulfur batteries. Unlike other solid additives used to trap polysulfides through physical and chemical interactions, it could effectively capture lithium polysulfides through chemical reaction between hexamethylene diisocyanate and lithium polysulfides at the electrode–electrolyte interface. A small amount of hexamethylene diisocyanate was enough to completely block the dissolution of lithium polysulfides into liquid electrolyte due to its high chemical reactivity, which enhanced the cycling stability of the lithium-sulfur battery while maintaining its high energy density. Our results demonstrate that the addition of hexamethylene diisocyanate to liquid electrolyte can provide an efficient strategy to address dissolution of lithium polysulfides and achieve good cycling stability in the high energy–density lithium-sulfur batteries.