Control of the porous structure and particle size is essential for improving the properties of polysilsesquioxane (PSQ) microspheres. Herein, using the strategy combining inverse suspension polymerization, two-step sol–gel- and polymerization-induced phase separation processes, micron-sized thiol-containing macroporous PSQ (TMPSQ) microspheres with controllable morphologies, adjustable particle diameters (4.9–17.3 μm), and pore sizes (40–3774 nm) were prepared. The morphology and size of the TMPSQ microspheres were characterized by SEM. The mercury intrusion method was employed to analyze the porous structure of the microspheres. The effects of the composition of the sol–gel disperse phase, the mass ratio of the sol–gel disperse phase to the oil continuous phase (WRW/O), and the Span 80 mass content in the oil continuous phase on the morphology, particle diameter and pore size of the TMPSQ microspheres were investigated. Results indicated that the composition of the sol–gel disperse phase determines the morphology and porous structure of the microspheres, and WRW/O and Span 80 content have remarkable impacts on the morphology and particle size of the microspheres. This study is beneficial to the design and fabrication of functional PSQ microspheres with desired properties and promising application prospects.