Irradiation effects on hardness and phase stability were investigated for an FeCr(Y, Ti)-ODS ferritic steel strengthened by Y-Ti-O nano-particles after irradiation with 6.4 MeV Fe3+ at room temperature (RT) up to nominal damages of 2, 10 and 50 dpa. With increasing local displacement damage up to ∼20 dpa, nano-sized oxide particles slightly shrank, while the corresponding number density drastically decreased by almost two orders of magnitude compared to that of before irradiation. It is considered that ballistic dissolution should be responsible for such reductions in the particle size and number density. Dislocation loops consisting of 1/2<111> type (>80%) and <100> type were observed under weak beam dark field (WBDF) imaging condition in the specimen irradiated to the nominal damage of 50 dpa. The average size and number density of all the dislocation loops were 2.8 ± 0.7 nm and (4.1 ± 0.7) × 1022 m−3, respectively, at the local damage of ∼72 dpa. Although the oxide particles were almost completely dissolved, nanoindentation hardness measurements revealed that the hardening went up continuously with increasing displacement damage and was estimated to be 1.63 ± 0.39 GPa by the Nix-Gao model at the nominal damage of 50 dpa. The irradiation hardening accompanied by the dissolution of oxide particles was interpreted in terms of loss of oxide particles, solid solution hardening and formation of fine dislocation loops. The contribution of dislocation loops observed by transmission electron microscopy (TEM) to the hardening was insufficient to overcome the loss of strengthening by dissolution, suggesting the importance of solid solution hardening and the larger strength factor of dislocation loops as a hardening contributor.