Osteoarthritis (OA) has been regarded as a lubrication deficiency related joint disease. Combination of both joint lubrication and drug intervention may provide a promising nonsurgical strategy for treatment of OA. Developing novel and simple approaches to fabricate superlubricating nanoparticles with drug release property is highly required. Herein, dopamine triggered one-step polymerization method was employed to fabricate polydopamine/poly(3-sulfopropyl methacrylate potassium salt) (PDA-PSPMA) conjugate coating on hollow silica (h-SiO2) nanosphere surfaces to engineer functional nanoparticles (h-SiO2/PDA-PSPMA). The as-prepared h-SiO2/PDA-PSPMA exhibits excellent aqueous lubrication performance on biomaterial substrates as well as natural bovine articular cartilage based on hydration effect of negatively charged PDA-PSPMA coating and rolling effect of h-SiO2 nanospheres. In vitro drug loading-release experiments demonstrate that PDA-PSPMA coating functionalized h-SiO2 nanospheres show high drug-loading and sustained-release capability of an anti-inflammatory drug, diclofenac sodium (DS). Such h-SiO2/PDA-PSPMA nanospheres can be potentially used as a synergistic therapy agent for OA treatment combining by simultaneous joint lubrication and drug release.