Entirely differing from the common templating-based multistep strategy for fabricating multifunctional hollow mesoporous silica nanoparticles (HMSN), a facile and template-free synthetic strategy has been established to construct a unique hollow/mesoporous organosilica nano-capsule (OSNC) concurrently encapsulating both isopentyl acetate (PeA) liquid and superparamagnetic iron oxides inside (denoted as PeA@OSNC). This novel material exhibits ultrasmall and uniform particle size (similar to 82 nm), high surface area (similar to 534 m(2).g(-1)), and excellent colloidal stability in aqueous solution. The oil-phase PeA with relatively low boiling point (142 degrees C) and high volatility not only plays a crucial role in formation of a large hollow cavity from the viewpoint of structural design but also enables the PeA@OSNC to act as an efficient enhancement agent in high-intensity focused ultrasound (HIFU) therapy. Moreover, the unique satellite-like distribution of Fe3O4 nanoparticles (NP) on the organosilica shell offered excellent magnetic resonance imaging (MRI) contrast capability of PeA@OSNC in vitro and in vivo. More importantly, such a novel theranostic agent has favorable biosafety, which is very promising for future clinical application in MRI-guided HIFU therapy.