Cu/Cu2O composite structures have been discovered to show sizable ferromagnetism (FM) with the potential applications in spintronic devices. To date, there is no consensus on the FM origin in Cu/Cu2O systems. Here, first principles calculations are performed on the interface structure to explore the microscopic mechanism of the FM. It is found that only the Cu vacancy (V(Cu)) adjacent to the outermost Cu2O layer induces a considerable magnetic moment, mostly contributed by 2p orbitals of the nearest-neighbor oxygen atom (O(NN)) with two dangling bonds and 3d orbitals of the Cu atoms bonding with the O(NN). Meanwhile, the charge transfer from Cu to Cu2O creates higher density of states at the Fermi level and subsequently leads to the spontaneous FM. Furthermore, the FM could be modulated by the amount of interfacial V(Cu), governed by the interfacial Cu diffusion with a moderate energy barrier (~1.2 eV). These findings provide insights into the FM mechanism and tuning the FM via interfacial cation diffusion in the Cu/Cu2O contact.