Transmission electron microscopy (TEM) and nanoindentation were performed in Hastelloy N alloy with three kinds ofirradiation mode: single He ions, He + Xe (3 dpa) ions and He + Xe (10 dpa) ions. TEM results showed the presence ofnano-sized irradiation-damage defects, such as helium bubbles, xenon bubbles, dislocation loops and precipitates. It wasfound that the helium bubble can grow up via absorbing vacancies, and the helium bubble shrinkage will be also occurreddue to the helium atoms re-solution. In the case of He + Xe (3 dpa) ions irradiation, the helium bubble growth via absorbingvacancies induced by subsequent Xe ion irradiation was more noticeable. As for the sample irradiated by He + Xe (10 dpa)ions, the ion irradiation enhanced helium atoms re-solution played an important role. Moreover, the helium atoms were moreeasily dissolved from small helium bubbles and the mechanisms behind them have also been shed light on. In addition, thedispersed barrier hardening and strengthening superposition models were used to predict the nanohardness increments producedby the different irradiation defects. The nanohardness increments measured by nanoindentation for irradiated sampleswere basically consistent with the calculated nanohardness increments.