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Nanoparticles based on porous silicon attract a lot of interest because of the outstanding properties of biocompatibility and biodegradability in the living environment. Wide opportunities of the surface modification, as well as efficient photoluminescence in the visible and infrared range, make them perfect agents for various theranostic applications, including targeted delivery of chemotherapeutic drugs. The current study is devoted to both theoretical and experimental investigation of sonoactivation of drug-loaded mesoporous silicon nanoparticles coated by biopolymers with the MHz-range ultrasound of moderate intensity. The role of two fundamental effects – acoustic cavitation and ultrasound-induced heat deposition – is taken into account. The presence of solid porous nanoparticles lowers the cavitation threshold in aqueous media due to the growth of air bubbles from nuclei and also leads to the heating of surrounding area due to the ultrasound energy absorption. In vitro experiments reveal the significant inhibition of cancer cell proliferation under the combined exposure to the nanoparticles and ultrasound radiation as compared to the intact group of cells. Investigation of the above physical effects at the nanoparticle/ bioenvironment interface has a great potential for the development of new strategies for the controlled drug release.