The self-healing mechanism has been newly applied in Ni superalloys to extend the creep lifetime during service. Quantitative selection criteria are proposed to screen the potential self-healing elements in Ni alloying system. Ti atoms and η-Ni3Ti precipitates are thus selected as the candidate healing atoms and the healing agent, respectively. The ideal composition interval for Ti to achieve the effective healing effects is computationally calculated as 0.076–0.1 mol fraction. On this basis, SHNi (self-healing Ni alloy) has been developed and compared with nSHNi (no self-healing Ni alloy). The creep lifetimes of SHNi alloys are observed 8–10 times higher than that of nSHNi alloys. Microstructure characterizations have shown that η-Ni3Ti healing agents in SHNi alloys can form site-specifically at the cavity sites during service. Meanwhile, the creep cavities in SHNi alloys present much smaller average sizes during creep, and the cavity growth rates are generally one magnitude lower compared to that of nSHNi alloys. The excellent creep properties of SHNi alloys can be well ascribed to their creep cavitation resistance brought by the self-healing behavior. The effectiveness of self-healing mechanism in improving the creep properties has proposed a new strategy in developing novel Ni superalloys.