This work reports the preparation of chitosan hollow nanospheres and their uses as the ultrasound-induced imaging agents. Reaction of chitosan to the 4-isocyanato-4′-(3,3-dimethyl-2,4-dioxo-azetidino)diphenylmethane modified silica nanoparticles forms silica@chitosan core shell nanoparticles. Removal of the silica cores with hydrofluoride generates the chitosan hollow nanospheres. Structures and morphology of the silica@chitosan core–shell nanoparticles and chitosan hollow nanospheres are characterized with an X-ray photoelectron spectroscopy and electron microscopies. Moreover, perfluoropentane is used an imaging gas to be filled into the chitosan hollow nanospheres. The gas-filled chitosan hollow nanospheres show ultrasonic-induced imaging behavior, demonstrating their potentials of applications in ultrasound-induced image.