Osteoarthritis is characterized by lubrication failure of the articular cartilage and severe inflammation of the joint capsule. Lubricating mesoporous silica nanoparticles (MSNs) have been developed for the treatment of osteoarthritis based on enhanced lubrication and local drug delivery. However, MSNs are difficult to degrade in vivo in a short time, resulting in potential toxic effect due to bioaccumulation. In this study, biodegradable MSNs (bMSNs) were prepared through an oil–water biphase stratification method, and modified with poly(2-methacryloyloxyethyl phosphocholine) (PMPC) to synthesize lubricating drug-loaded nanoparticles (bMSNs–NH2@PMPC) by photopolymerization. The in vitro degradation test demonstrated that the bMSNs and bMSNs–NH2@PMPC almost degraded within 7 days. The tribiological test showed that the lubrication property of the bMSNs–NH2@PMPC was greatly improved, with a reduction of 50% in the friction coefficient (COF) compared with the bMSNs. It was attributed to hydration lubrication mechanism by which a tenacious hydration layer is formed surrounding the zwitterionic headgroups (N+(CH3)3 and PO4- ) in PMPC polyelectrolyte polymer. Additionally, the bMSNs–NH2@PMPC maintained excellent lubrication property under degradation and achieved sustained drug release behavior compared with the bMSNs. In summary, the biodegradable bMSNs–NH2@PMPC developed in this study with the properties of enhanced lubrication and drug delivery may be a promising approach for osteoarthritis therapy.