The strong metal–support interaction over Pt/TiO2 catalysts, which were prepared by depositing size-specified Pt colloids (2–6 nm) onto anatase TiO2 nanosheets dominated by the reactive {001} facets, was featured by the formation of Pt3Ti intermetallic alloy and showed a size-dependent effect. After H2 reduction at 773 K, bulk Pt–Ti alloys in a mixture of disordered and ordered phases were readily formed over 2 nm Pt particle, while Pt3Ti intermetallic alloys, with a thickness of up to 6 atomic layers, were observed on 4–6 nm Pt particles, showing as a Pt3Ti@Pt core–shell architecture where the Ti atom substituted the Pt atom periodically and interacted with the Pt atom electronically. By further raising the temperature for H2 reduction to 873 K, the 2–6 nm Pt particles turned into well-crystallized Pt3Ti intermetallic alloys. Both bulk Pt–Ti and Pt3Ti intermetallic alloys suppressed considerably the chemisorption of H2 and CO but dramatically promoted the selectivity for hydrogenating the C═O bond in acetophenone.