The irradiation hardening behavior of reduced-activation ferritic steels after single Fe-ion beam irradiation and dual-ion (Fe ion and He ion) beam irradiation experiments was investigated with nanoindentation tests. The ion-irradiation experiments were conducted at 563 K with 6.4 MeV Fe3+ ions up to 3 dpa at a 600 nm depth from the irradiated surface. Furthermore, these experiments were conducted with and without simultaneous energy-degraded 1 MeV He+ ions up to 300 appm. The materials used were F82H, F82H + 1Ni, and F82H + 2Ni to investigate the effect of Ni addition on the irradiation hardening behavior. The measured nanoindentation hardness was converted to the bulk-equivalent hardness based on a combination of the Nix-Gao model to explain the indentation size effect and the composite hardness model to explain the softer substrate effect of the nonirradiated region beyond the irradiated depth range. It is clearly shown that the Ni addition enhances the irradiation hardening of F82H. The bulk-equivalent hardness is compared with the experimentally obtained Vickers hardness of F82H steels after neutron irradiation. The effect of simultaneously implanted helium on the irradiation hardening is negligible in the investigated irradiation conditions.