Sulfide bond incorporated organosilica particles have been broadly applied to versatile biomedical appli-cations, wherein the uniformity of particles and the sulfur content significantly dictate the ultimate per-formance. Unfortunately, due to the difficulty in controlling the chemical behavior of organosilica precursors in a sol & ndash;gel process, challenges still exist in developing a facile and green synthetic approach to fabricate organosilica particles with good dispersity and high sulfur content. In the present work, by extending the classic St & ouml;ber method, a surfactant-free synthesis of monodispersed organosilica particles with pure sulfide-bridged silsesquioxane framework chemistry is reported for the first time. By simply tailoring the ethanol-to-water ratio and amount of catalyst, the size of disulfide-bridged organosilica par-ticles can be tuned from-0.50 to-1.20 mm. Moreover, this approach can be employed to prepare tetra-sulfide bridged silica nanoparticles with an extremely high sulfur content of 30.7 wt% and negligible cyto-toxicity. Notably, taking advantage of this extended St & ouml;ber method, both hydrophilic (methylene blue) and hydrophobic (curcumin) molecules can be in-situ encapsulated into tetra-sulfide bridged silica nanoparticles, whose glutathione-triggered biodegradability is also demonstrated. Collectively, the inno-vative synthetic approach and organosilica particles developed in this work are expected to open up new opportunities in hybrid materials fabrication and bio-applications. (c) 2021 Elsevier Inc. All rights reserved. Sulfide bond incorporated organosilica particles have been broadly applied to versatile biomedical applications, wherein the uniformity of particles and the sulfur content significantly dictate the ultimate performance. Unfortunately, due to the difficulty in controlling the chemical behavior of organosilica precursors in a sol?gel process, challenges still exist in developing a facile and green synthetic approach to fabricate organosilica particles with good dispersity and high sulfur content. In the present work, by extending the classic St?ber method, a surfactant-free synthesis of monodispersed organosilica particles with pure sulfide-bridged silsesquioxane framework chemistry is reported for the first time. By simply tailoring the ethanol-to-water ratio and amount of catalyst, the size of disulfide-bridged organosilica particles can be tuned from -0.50 to -1.20 mm. Moreover, this approach can be employed to prepare tetrasulfide bridged silica nanoparticles with an extremely high sulfur content of 30.7 wt% and negligible cytotoxicity. Notably, taking advantage of this extended St?ber method, both hydrophilic (methylene blue) and hydrophobic (curcumin) molecules can be in-situ encapsulated into tetra-sulfide bridged silica nanoparticles, whose glutathione-triggered biodegradability is also demonstrated. Collectively, the innovative synthetic approach and organosilica particles developed in this work are expected to open up new opportunities in hybrid materials fabrication and bio-applications.