<p>The microstructural evolution and mechanical property changes of a nickel-based alloy (Inconel 617) subjected to heavy ion irradiation are investigated to simulate the irradiation effect of the nickel-based core structure materials under in-pile service conditions. Transmission electron microscopy (TEM) analysis combined with nanoindentation measurements is conducted. TEM characterization results indicate that the microstructural changes induced by irradiation mainly involve the formation of irradiation defects in the Ni matrix and the instability of the γ′precipitates. Irradiation-induced defects observed in the Ni matrix mainly include faulted loops with a stripe shape and circular contrast. In addition, the occurrence of disordering and dissolution in γ′ precipitates by irradiation is confirmed, in which order-to-disorder transformation is dominant under the present irradiation conditions relative to dissolution. Nanoindentation results demonstrate significant irradiation-induced hardening in all the specimens. Furthermore, the dispersed barrier hardening model is applied to correlate the microstructure and mechanical properties in ion-irradiated Inconel 617. Although the disordering of the γ′ phase results in softening in the material, the presence of irradiation loops significantly contributes to the hardening of materials. Additionally, under high-temperature irradiation, the hardening contribution from the dissolution of γ′ phase and the interaction of dislocation movement has to be considered.</p> Graphical Abstract <p></p>