The liquid-phase hydrogenation of diphenylacetylene (DPA) over 1 wt% Pd/Al2O3 catalysts with the mean palladium cluster size varying from 1.9 to 20 nm was studied at 5 bar H2 pressure and 25 °C. Hydrogenation of the triple bond was found to be structure sensitive and turnover frequency increased as Pd cluster size increased, while TOF in hydrogenation of the intermediate stilbene was essentially independent on the cluster size. Selectivity to stilbene was rather high (90–94%) and tends to increase with an increasing of Pd particle size. A reaction network was proposed for diphenylacetylene hydrogenation involving formation of cis- and trans- stilbene and their subsequent hydrogenation. The effect of Pd nanoparticle size on the hydrogenation kinetics was analyzed and discussed using a geometric approach based on the respective contribution of low (edges, corners) and highly coordinated sites (terraces) for a cubooctahedral shape of metal clusters. A quantitative description of the concentration dependences was performed incorporating the Pd particle size in the rate equations through changes in dispersion and the ratio of sites of different coordination. An excellent correspondence between theory and experiments was demonstrated.