Bioactive glasses (BG) have emerged as fascinating materials for bone regeneration, owing to their unique properties of bone-bonding, osteogenesis and angiogenesis potential. However, BG still suffer from the limitation of being not able to induce rapid bone regeneration and vascularization. The integration of biomolecules that can accelerate osteogenesis and angiogenesis with BG is thus an auspicious strategy towards more efficient bone regeneration. Hollow mesoporous nanoparticles are attractive materials for drug delivery, due to their morphological characteristics. Hollow mesoporous bioactive glass nanoparticles (HMBGN) are therefore considered to be attractive carriers of biomolecules for bone regeneration. However, the synthesis of HMBGN is still challenging. HMBGN can be synthesized by using soft templates through sol-gel routine, but the synthesized HMBGN mostly exhibit inhomogeneous shape and size. In this study, we developed a multi-step process to synthesize HMBGN with uniform shape and size. Solid silica nanoparticles were synthesized firstly by using the Stöber method to serve as hard templates to assembly CTAB and silica species around them. The formed hybrid nanoparticles then underwent a selected etching process to remove the solid cores prior to the incorporation of Ca ions by soaking the etched particles in calcium salt solution. HMBGN were then achieved by heating the soaked nanoparticles. These HMBGN exhibited homogenous size and spherical shape with mesoporous shell. The particle size and shell thickness of HMBGN could be tailored by tuning the size of cores and added amount of silica precursor, respectively, while the Ca content could be tuned by changing either the concentration of soaking solution or soaking time. HMBGN exhibited a large specific surface area and pore volume, as well as showing a satisfactory apatite-forming ability. These HMBGN are therefore promising materials carrying biomolecules for bone regeneration.