Abstract P(EMA- co-HEA)/SiO 2 nanocomposites with silica contents in the range of 0–30 wt% were prepared by co-polymerization of the organic monomers during the simultaneous sol–gel polymerization of the silica precursor. The ability of the hybrids to form hydroxyapatite (HAp) on their surfaces was tested in vitro by soaking the samples in a simulated body fluid (SBF) solution for different times up to 35 days. On the one hand, the composition and morphology of the HAp layer formed were characterized by SEM, EDS, FTIR and XRD; on the other, the exchange of soluble silicates and calcium and phosphate ions, and the structural changes taking place in the nanohybrids when immersed in SBF were analyzed by SEM/EDS. This is, up to our knowledge, the first time the HAp nucleation mechanism has been proposed for organic-silica nanohybrids and correlated with their respective nanostructures. The results revealed that the formation of a HAp coating was in all cases limited by the nucleation induction time, but the mechanism and rate of HAp nucleation were found to be different depending on the nanostructure of the samples, which differs, in turn, with the silica content as a consequence of the differing connectivity of the silica network. The nanohybrids with silica contents in the range of 10–20 wt% proved to be the most suitable for the development of bioactive synthetic scaffolds for bone or other mineralized tissues.