Size-dependent reaction of nickel-doped silver cluster cations (AgN-1 Ni+: N = 5-14) was investigated for oxygen as the reactant molecule. A dramatic drop in the reactivity observed for N >= 9 is attributed to the encapsulation of the nickel atom, i.e., screening the active site at larger sizes. The reactivity minimum observed at N = 10 is ascribed to the closed electronic shell of Ag9Ni+ formed by 18 valence electrons from Ag5s, Ni4s, and Ni3d, suggesting delocalized d electrons.