With silk fibroin and vancomycin (VCM) as carrier and drug model, respectively, we prepared silk fibroin microspheres (SFM) with different concentration using the water-in-oil emulsion solvent diffusion method. We further developed VCM loaded calcium sulfate hemihydrates (CSH)/SFM artificial bone composites. In this study, surface morphology of the materials was observed using scanning electron microscope (SEM). Structure of the materials was studied with Fourier transform infrared spectroscopy (FTIR). Antibacterial activity of the materials was validated with the inhibition zone test. Drug release property of materials was evaluated using ultraviolet/visible spectrophotometry. Mechanical property of the materials was tested using computer-controlled electronic universal testing machine. The results showed that silk fibroin concentration had no significant effect on molecular conformation and antibacterial property of the SFM. The average diameter of SFM increased and the release rate decreased gradually as the silk fibroin concentration increased. The release rate decreased and the compressive fracture work increased as the silk fibroin concentration increased when adding SFM to CSH. This composite had partly corrected the disadvantages of CSH including the high brittleness and initial burst release. The research would have a good application foreground in the clinical treatment of infectious bone defect.