Periodic mesoporous organosilicas (PMOs) with homogeneously incorporated organic groups, highly ordered mesopores, and controllable morphology have attracted increasing attention. In this work, one-step emulsion approach for preparation of hollow periodic mesoporous organosilica (HPMO) nano spheres has been established. The method is intrinsically simple and does not require any sacrificial templates, corrosive and toxic etching agents. The obtained HPMO nanospheres have high surface area (similar to 950 m(2) g(-1)), accessible ordered mesochannels (similar to 3.4 nm), large pore volume (similar to 3.96 cm(3) g(-1)), high condensation degree (77%), and diameter (similar to 560 nm), hollow chamber size (similar to 400 nm), and shell thickness (similar to 80 nm). Furthermore, cytotoxicity show the cell viability is higher than 86% after incubating with the HPMO nanospheres at a concentration of up to 1200 mu g mL(-1) for 24 h. The hemolysis of HPMO nano spheres is lower than 1.1% at concentrations ranging from 10 to 2000 mu g mL(-1). The lower hemolysis and cytotoxicity make the HPMO nanospheres great promise for future biomedical applications. (C) 2016 Elsevier Inc. All rights reserved.