This article reports a general method to prepare hollow mesoporous silica nanoparticles with tailored morphology. The method is based on selective dissolution of porous cores of solid silica shell/porous silica core nanoparticles under mild conditions without the need for corrosive or toxic etchants. First, core-shell nanospheres or nanorods are prepared in a one-pot reaction. Then, mesoporous cores of the nanoparticles are selectively dissolved by incubating them in phosphate buffered saline (PBS) at 65 °C for one day. Surprisingly, shells of the resulting hollow particles contain both small and large mesopores which makes the particles very suitable for adsorption and desorption of a wide range of molecules. In addition, we proposed a mechanism for selective dissolution of porous cores of the core-shell nanoparticles.