Aiming at identifying the effects of Pd ensemble and cluster size on the selectivity and activity of C2H2 selective hydrogenation over Pd-modified Cu nano-cluster catalysts, the catalytic performance of C2H2 selective hydrogenation over different cluster sizes of Pd-modified Cu catalyst with different Pd ensemble are examined using density functional theory calculations. A new evaluation method of the C2H4 selectivity is defined. The results indicate that the promoter Pd cannot improve C2H4 selectivity and activity over the small-sized Cu-13 and the large-sized Cu-55 clusters. Only when Cu catalyst has a moderate size such as Cu-38 cluster, the Pd ensemble composed of outer shell with 6 coordination and its contiguous inner-layer Pd atoms can significantly improve C2H4 selectivity and activity. This study provides a theoretical clue for the design of highly efficient and cost-effective noble promoter-modified Cu-based catalysts by controlling the cluster size and the promoter ensemble for C2H2 selective hydrogenation.