Large-pore periodic mesoporous organosilica (PMO) hollow spheres with controllable pore size and high pore volume (2.5 cm3 g−1) were successfully synthesized at low-temperature (∼15 °C) by using the triblock copolymer Pluronic F127 as a template and 1,3,5-trimethylbenzene (TMB) as a swelling agent in the presence of inorganic salt (KCl). Transmission electron microscopy (TEM) measurements show that the PMO hollow spheres are uniform and well dispersed, and the composites have a large wall thickness. The influence of TMB, KCl, CTAB contents and media acidity on the mesostructure was systematically studied. The pore size (9.8–15.1 nm) of the hollow spheres can be gradually expanded by increasing TMB content together with a relatively high acidity. By controlling the content of CTAB, successive structural transformation from hollow sphere to wormlike mesostructure and eventually to ordered body-centered cubic (space group of Im-3m) mesostructure is observed. Our results reveal that the hydrophobicity of bis(triethoxysilyl)ethane (BTSE) and low-temperature approach contribute to the slow hydrolysis rate of silica precursors, which leads to weak interaction between individual TMB/F127 micelles and silicate oligomers. Furthermore, the salting-out effect of KCl may influence the swelling capacity of individual micelles as well as decrease the critical micelle concentration and critical micelle temperature, resulting in the formation of PMO hollow spheres from the assembly of individual TMB/F127 micelles with silicate oligomers. The composites exhibit efficient adsorption capacity (703 mg g−1) for toluene, suggesting they are a potentially useful adsorbent for removal of volatile organic compounds. The PMO hollow spheres allow biomolecules with large molecular weight to diffuse in, and show superior encapsulation capacity of bovine serum albumin (BSA) molecules (∼585 mg g−1) over other porous materials.