One-pot hard/soft template-free synthesis of hollow structured mesoporous silica particles (H-MSPs) with enlarged pore sizes was developed. By a simplified in situ hydrothermal treatment under mild conditions (70 °C), a hollow interior evolution to a final size of ~150 nm was successfully induced for the as-prepared particles from the sol–gel synthesis solution. The particles were evenly spherical with an average particle diameter of 350 nm, as well as a mean pore size of 5 nm in the mesoporous shell. Pore-swelling agents and aminosilane were demonstrated to contribute to the chemical irregularities in the silica network formation during particle growth, consequently leading to selective dissolution of the interior silica.