Unveiling the mystery of the contribution of nonsurface or noninterface sites in a catalyst to its catalytic performance remains a great challenge because of the difficulty in capturing precisely structural information (surface plus inner) encoded in the catalyst. This work attempts to elucidate the critical role of the internal vacancy in an atomically precise 24-atom gold cluster in regulating the catalytic performance on the hydrogenation reaction of CO2. The experiment results show that the Au-24 cluster with internal vacancy can mitigate sintering and exhibit high catalytic activity under relatively harsh reaction conditions, in contrast to the structurally similar Au-25 cluster without internal vacancy. Our computational study suggests that the internal vacancy in Au-24 provides the cluster with much more structural flexibility, which may be crucial to resisting the aggregation of the cluster and further postponing the deactivation. The hydrogenation and coupling stages of the reaction intermediates are proposed to explain the potential reaction pathway of CO2 with H-2 on the Au-24 catalyst with internal vacancy.