Harmful bacteria have seriously threatened human health and wealth for a long time. Herein, a multifunctional drug delivery system based on UiO-66 was fabricated, and it showed potent synergistic antibacterial effects when used in conjunction with photodynamic therapy and chemotherapy. First, UiO-66-NH2 was prepared via a facile solvothermal method. Then, carboxylic zinc phthalocyanine, a broad-spectrum photosensitizer, was connected to UiO-66-NH2 by amidation. Next, synergistic chemical antibiotic linezolid was loaded in the pores, and lysozyme was coated on the surface by electrostatic interactions. In vitro antibacterial experiments were then carried out to evaluate the antibacterial effects of this system against three kinds of bacteria, Staphylococcus aureus, Escherichia coli, and methicillin-resistant S. aureus (MRSA). The combination of lysozyme, linezolid, and singlet oxygen generated by irradiation of the photosensitizers resulted in a potent antibacterial effect against S. aureus, E. coli, and even MRSA, which demonstrates the synergistic antibacterial efficacy of photodynamic therapy and chemotherapy.