Abstract: Key equipment is unavoidable to encounter friction loss and severe wear failure under extreme conditions during the production of major apparatus, including high energy consumption, high safety risk, and low utilization efficiency, which poses significant obstacles to the advancement of manufacturing technology and enterprise cost management. Lubricating grease as a common lubricant for large machinery and equipment, playing a vital role in the friction reduction and anti-wear of mechanical equipment. Traditional grease composed of two independent dispersants of thickener and additive faces numerous technical barriers such as environmental adaptability, performance stability and product refinement. A crucial prerequisite for obtaining high performance interface lubrication is to regulate the composition and structure of thickener for grease. On the basis of the intrinsic structure and interfacial lubrication characteristics of grease, regulating the composition and structure of thickeners is essential for the development of high-performance industrial lubricating greases. A MoS₂-supported polytetrafluoroethylene (PTFE) hybrid system was fabricated using a single-step hydrothermal procedure. Molybdenum disulfide functionalized polytetrafluoroethylene (PTFE/MoS₂) hybrid was obtained by coupling polarizable Mo atoms with oxygen-containing functional groups on the surface of an activated PTFE matrix. Using this as a thickener to modulate polyalphaolefin base oil (PAO40) produced a PTFE/MoS₂ lubricating grease that substantially reduced friction (33.3%) and wear under four ball point contact. The PTFE/MoS₂ thickener possessed superior thickening and lubrication properties. MoS₂ possessing interlayer slip effect and the formation of interfacial frictional chemical films were primarily responsible for the outstanding tribological performance. The prepared molybdenum disulfide-functionalized polytetrafluoroethylene thickener provided ideas for the creation of new high-performance grease.