The effective modulation of pore sizes for nanoporous silica nanoparticles still remains a great challenge not satisfactorily solved. In this paper, the pore sizes in the shell of hollow silica nanocapsules are well-tuned by a reversible Si-O bond breakage and reformation process under mildly alkaline conditions (e.g., Na(2) CO(3) solution). The pores in nanosized hollow silica capsules can be modulated from 3.2 nm to larger than 10 nm by a novel, surfactant-directing alkaline-etching (SDAE) strategy. Interestingly, the pores can be fully filled through the regrowth of the dissoluted silicates by bonding to silanols (Si-OH) on the wall surface to generate the nonporous hollow silica nanocapsules. The large-sized pore hollow silica nanocapsules exhibit excellent siRNA-loading capabilities and intracellular transfection efficiencies in vitro. In addition, the large pores in the shell of hollow silica nanocapsules are explored as channels for collecting superparamagnetic, small-sized Fe(3) O(4) nanoparticles as contrast agents for magnetic resonance imaging, initiating a special approach towards pore-size modulation and multifunctionalization of silica-based nanostructural materials for nanobiomedical applications.