Infected bone defects are normally regarded as contraindications for bone repair. In the present study, a hollow mesoporous structure of silica (SiO2) microspheres was first synthesized and loaded with ibuprofen (IBU). Poly(1,8-octanediol-co-citrate) (POC) and β-tricalcium phosphate (β-Ca3(PO4)2, β-TCP), together with IBU-loaded SiO2 were fabricated by a 3D printing technique based on the Freeform Fabrication System with Micro-Droplet Jetting (FFS-MDJ). The physiochemical properties, compressive modulus, drug release behavior, antimicrobial properties and cell response of the composite scaffold were systematically investigated. The developed IBU-loaded SiO2/β-TCP/POC scaffolds presented a highly interconnected porous network, macropores (350-450 μm) and mesopores (3.65 nm), as well as proper compressive modulus and biocompatibility. The addition of hollow SiO2 microspheres was found to decrease the burst release and increase the cumulative release amount of IBU. In addition, IBU-loaded SiO2/β-TCP/POC showed a long-term effect on inhibiting E. coli growth by agar diffusion. The result indicated that the IBU-loaded SiO2/β-TCP/POC scaffold, with a hierarchically macro/mesoporous, highly interconnected pore structure and an effective antimicrobial property, demonstrates promise for bone regeneration in the clinical case of infected bone defects.