β-Tricalcium phosphate (β-TCP) is widely used, along with bone-derived growth factor, due to its poor osteogenic ability. Mesoporous silica (MPS)-coated β-tricalcium phosphate (β-TCP) granules were prepared to improve protein loading capability, and in vitro evaluations of this material were carried out. β-TCP powder containing 2 wt% Al2O3 and 6 wt% SiO2 was prepared via mechanochemical synthesis. A sodium alginate solution containing β-TCP powder was transferred into a calcium chloride solution, and the obtained spherical beads were heated at 1100 to 1300°C to produce TCP granules. The X-ray diffraction (XRD) profile of the β-TCP granules containing 2 wt% Al2O3 and 6 wt% SiO2 was identical to that of the single β-TCP phase when heated to 1300°C. The compressive strengths of the TCP granules prepared using alginate were remarkably improved compared with those of TCP granules prepared using a pan-type granulator. A silica interlayer was formed on the β-TCP granules containing 2 wt% Al2O3 and 6 wt% SiO2 via magnetron sputtering prior to the coating of the MPS. MPS coatings on β-TCP granules containing 2 wt% Al2O3 and 6 wt% SiO2 was carried out by a dip-coating method after silica interlayer coatings, and the β-TCP granules containing 2 wt% Al2O3 and 6 wt% SiO2 were covered by the MPS particles. A silica interlayer may offer bonding between the β-TCP granules and MPS coating. The Alamar blue assay of the MPS-coated TCP granules exhibited excellent cell viability as well as a high protein-adsorption capacity.