The photocatalytic degradation of acetonitrile was carried out in liquid-solid regime in a batch reactor by using two types of commercial TiO2 powders (Merck and Degussa P25) as photocatalysts. The concentration of acetonitrile and non-purgeable organic carbon (NPOC) were monitored. The initial rate of acetonitrile conversion was found higher on TiO2 Merck than on TiO2 P25. FT-IR spectroscopy was used to investigate the molecular features of the adsorption and photo-oxidation of acetonitrile on the two TiO2 powders in a fully surface hydrated form. Acetonitrile was found adsorbed on Ti4+ surface ions and hydroxyl groups for both types of TiO2. This interaction appeared fully reversible in the case of the Merck photocatalyst, whereas acetonitrile was more strongly stabilized on Ti4+ ions of TiO2 P25. Furthermore, the adsorption of CD3CN...Ti4+ on this type of photocatalyst resulted in the formation of acetamide-like species, because of the presence of nucleophilic surface O2- and hydroxyl groups. The formation of these species, strongly bound to the TiO2 surface and recalcitrant to the photo-oxidation, could result in the poisoning of a part of the photocatalytic sites of TiO2 P25, accounting for its lower initial acetonitrile conversion rate.