Nanoparticles represent one of the most promising materials as they have found application in bionanotechnology for enhanced imaging, diagnosis, and treatment of several diseases. Silica coating is widely used to improve colloidal stability and the binding affinity of nanoparticles for various organic molecules, such as cell-penetrating peptides (CPPs). The functionalization of the silica coating by CPPs is very promising, since it enhances the uptake of the nanoparticles due to the intrinsic ability of the CPPs to cross the cellular membrane. However, molecular level phenomena characterizing the CPPs interaction with silica-coated nanoparticles are not clarified yet. In this work, classical molecular dynamics has been used to shed light on the adsorption mechanism of several CPPs onto silica surfaces, in order to highlight the influence of the surface ionization's state on the adsorption mechanism. Our data highlight how the cationic peptides strongly interact with the anionic silica surfaces by H-bond formation between charged residues and the negatively charged siloxide groups, as well as ion pairing between the surfaces and the N-termini residues. Moreover, thanks to metadynamics simulations the CPP-silica binding affinity has been quantified. The free energy profile description allows providing insight into the relationship between ionization of silica nanoparticles and binding selectivity/specificity to CPP.