Mesoporous hollow silica nanospheres with uniform particle sizes of 31–33 nm have been successfully synthesized by cocondensation of tetramethoxysilane (TMOS) and alkyltrimethoxysilanes [RSi(OR)₃], where the latter also acts as a porogen. ABC triblock copolymer micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS–PVP–PEO) with a core–shell–corona architecture have been employed as a soft template at pH 4. The cationic shell block with 2-vinyl pyridine groups facilitates the condensation of silica precursors under the sol–gel reaction conditions. Phenyltrimethoxysilane, octyltriethoxysilane, and octadecyltriethoxysilanes were used as porogens for generating mesopores in the shell matrix of hollow silica and the octadecyl precursor produced the largest mesopore among the different porogens, of dimension ca. 4.1 nm. The mesoporous hollow particles were thoroughly characterized by small-angle X-ray diffraction (SXRD), thermal (TG/DTA) and nitrogen sorption analyses, infra-red (FTIR) and nuclear magnetic resonance (¹³C-CP MAS NMR and ²⁹Si MAS NMR) spectroscopies, and transmission electron microscopy (TEM). The mesoporous hollow silica nanospheres have been investigated for drug-delivery application by an in vitro method using ibuprofen as a model drug. The hollow silica nanospheres exhibited higher storage capacity than the well-known mesoporous silica MCM-41. Propylamine functionalized hollow particles show a more sustained release pattern than their unfunctionalized counterparts, suggesting a huge potential of hollow silica nanospheres in the controlled delivery of small drug molecules.