Mixed Ta2O5/SiO2 nanoparticles are attractive for their high radiopacity as transparent dental fillers and even for bone replacement. The effect of Ta2O5 content on surface acidity of flame-made Ta2O5/SiO2 particles was studied by NH3 temperature-programmed desorption (TPD). Emphasis was placed on the influence of particle composition on surface functionalization by a common surfactant, γ-methacryloxypropyltrimethoxysilane (MPS). Such surface modified particles were analyzed by thermogravimetric analysis, 13C- and 29Si-NMR and FT-IR spectroscopy. Compared to pure silica, Ta2O5/SiO2 particles exhibited significantly higher surface acidity, thereby facilitating functionalization of their surface hydroxyl groups without a catalyst (e.g. n-propylamine, PA). The surface modifier structure was only slightly influenced by the Ta2O5 presence compared to pure SiO2. The long term hydrolytic stability of such surface modified Ta2O5/SiO2 particles was comparable to pure silica up to 80 days at 22 °C indicating stable bonding between particle surface and modifier.