Compared to other well-developed synthetic methods, we developed a novel "phase separation inside monomer droplets" strategy in miniemulsion polymerization to fabricate hollow mesoporous silica microspheres (HMSMs) with an average diameter of similar to 500 nm. This one-step process produced high HMSMs yield and a solid content of above 3.4%. The flexibility of the proposed method was further demonstrated to fabricate amino groups-modified HMSMs (HMSM-NH2) via co-condensation of tetraethylorthosilicate and adding 3-aminopropyltriethoxysilane confined in oil phase. Waterborne polyurethane-grafted HMSM-NH2 (HMSM-NH2-g-WPU) particle brushes were prepared by chain extention reactions between HMSM-NH2 and NCO groups-terminated PU prepolymer during the self-emulsification process. HMSM-NH2-g-WPU coating provided an opacity of 90% with only 4 wt % of HMSM-NH2 addition and exhibited a gloss of 3.1 (60 degrees) with 5 wt % HMSM-NH2 addition. The one-pot miniemulsion production of HMSM-NH2 combined with widely used industrial production lines of WPU enables its excellent industrial scalability with promising applications in leather finishing, paper printing, and printing coatings.