Porous silicon micro-particles (micro-pSi) with size in the range of 1-10 μm are obtained by etching of silicon wafers followed by sonication. The derivatization of the micro-pSi surface by wet chemistry (silylation and coupling with a diamine) yields an interface, which exposes negative (carboxylic) or positive (amine) groups at pH 7.4. The surface modification, beyond the introduction of groups for the drug loading by covalent or electrostatic interactions, stabilizes the intense orange luminescence characteristic of the silicon nano-crystallites. Derivatization by amines introduces also a second emission in the blue region, which follows a different excitation pathway and can be attributed to the interface defects. The micro-pSi are efficiently internalized by human dendritic cells and do not show any toxic effect even at a concentration of 1 mg mL. The intrinsic luminescence of the differently functionalized micro-pSi is preserved inside the cells and permits the selective and efficient tracking of the microparticles without using molecular tags and thus leaving the organic coating available for the interaction with the drug. The results obtained suggest that the functionalized micro-pSi are an efficient platform for simultaneous imaging and delivery of therapeutic agents to the disease site.