One advanced synthesis strategy for monodisperse silica cross-linked micellar core-shell nanoparticles (SCMCSNs) involves the use of organosilane termination agent RnSi(OR')(4-n). In this study, we investigated the effects of the organosilane termination agent in the formation of SCMCSNs. Experimental data (synthesis results, Si-29 MAS NMR, molecule probe fluorescence spectra, etc.) from a synthesis system with Pluronic F127 as the template indicate that organosilane either covers or reacts with the surface Si-OH groups of nanoparticles. The reduction of reactive surface Si-OH groups helps to stabilize nanoparticles by avoiding aggregation. The terminating behavior of organosilane is determined by its molecular structure, including (1) the value of n, (2) the length of hydrocarbon chain R, and (3) the charge of R. Effective organosilane termination agents are also applicable to other synthesis mixtures such as the systems using Si(OC2H4OH)(4) as the silica source or F108 or Brij 700 as the template. Furthermore, we can obtain monodisperse nanoparticles by using the trisodium salt of triacetic acid N-(trimethoxysilylpropyl)ethylenediamine (TANED), which acts not only as a termination agent for the successful synthesis of SCMCSNs but also as a functional group to improve the performance of SCMCSNs in potential applications.