In this work, we have quantified the functionalization of some porous silicon multilayers that optically act as Bragg reflectors: 1.3 × 10−3 mol/g, corresponding to 3.25 nmol/cm2, of a ten base oligonucleotide has been estimated by a chemical procedure, based on the dimethoxytrityl monitoring. The oligonucleotide has been synthesized directly on two different porous silicon structures, one oxidized by a thermal treatment, the other by a chemical process based on exposure to I2/pyridine. We have also monitored the oligonucleotide synthesis by a label-free technique: a 11 nm red-shift of the optical spectrum can be observed by spectroscopic reflectometry.