Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear and ultimately irreversible damage. This situation is particularly challenging for early-stage OA, as current bio-lubricants lack precise targeting for small inflammatory lesions. In this work, an antibody-mediated targeting hydrogel microspheres (HMS) is developed to precisely lubricate the local injury site of cartilage and prevent the progression of early OA. Anti-Collagen type I (Anti-Col1) is an antibody that targets cartilage injury sites in early OA stages. It is anchored on a HMS matrix made of Gelatin methacrylate (GelMA) and poly (sulfobetaine methacrylate) (PSBMA) to create targeted HMS (T-G/S HMS). The T-G/S HMS's high hydrophilicity, along with the dynamic interaction between its surficial Anti-Col1 and the Col1 on cartilage injury site, ensures its precise and effective lubrication of early OA lesions. Consequently, injecting T-G/S HMS into rats with early OA significantly slows disease progression and reduces symptoms. In conclusion, the developed injectable targeted lubricating HMS and the precisely targeted lubrication strategy represent a promising, convenient technique for treating OA, particularly for slowing the early-stage OA progression.