A flexible aerogel polymerized from methyltrimethoxysilane (MTMS) shows great promise as a high-performance insulator owing to its substantially low thermal conductivity and mechanical flexibility, attributed to its porous microstructure and organic–inorganic hybridization, respectively, which promote its industrial applications. Conventionally, the cationic surfactant n-hexadecyltrimethylammonium chloride (CTAC) is utilized to experimentally control the nanoscale microstructure and, consequently, the flexibility of the MTMS aerogel; however, the mechanism through which CTAC prevents MTMS aggregation in the solution is not yet fully understood. This study unravels the role of CTAC in preventing MTMS aggregation in aqueous solution using both classical and reactive molecular dynamics simulations. We found that CTAC molecules can form self-aggregates even when the polymerization of MTMS progresses and then the MTMS-derived oligomer turns to be hydrophobic in aqueous solution. In summary, the self-assemblies of CTAC disperse among the MTMS associations and effectively prevent MTMS clustering, and this is considered as the key mechanism underlying the formation of a flexible microstructure of the hybrid aerogel.