Multifunctional nanophotosensitizers (UPM) composing of upconversion nanoparticles NaYF4:Yb,Tm@NaGdF4:Yb, polydopamine, polyethyleneimine and MnO2 were prepared by reverse microemulsion method. The morphology, chemical composition, optical properties and size distribution of the obtained products were characterized by TEM, FTIR, UV-Vis, PL and DLS. Then, the reactive oxygen species generation ability and the loading and release of tetracycline hydrochloride (TC) from UPM were measured, and the antibacterial performance of TC-loaded nanophotosensitizers (UPM/TC) under near-infrared (NIR) light irradiation was investigated. The results showed that the nanophotosensitizers showed catalase-like activity and the capacity of producing hydroxyl radical and singlet oxygen in presence of H2O2 as exposed to NIR light. The loading capacity of TC in UPM was 22.6%, and the in vitro release of TC was pH-sensitive. After exposure to 980 nm NIR light (1.2 W/cm2) for 10 min , UPM/TC at a mass concentration of 0.8 g/L exhibited 99.7% bacterial inactivation to E. coli and better antibacterial performance than free TC or UPM by virtue of the synergistic effect of photodynamic and antibiotic sterilization.