Abstract: The initial microstructure and irradiation induced hardening of ODS-Eurofer were studied in this work. Transmission electron microscopy (TEM) was used to characterize the microstructure of ODS-Eurofer. Nano-particles with the diameter ranging from several to tens of nanometers and larger particles with core-shell structure (diameter larger than 100 nm) were both observed. Dislocation line was observed to be pinned by nano particles. 5 MeV Fe²⁺ ions were implanted into ODS-Eurofer up to an irradiated damage of 25 dpa to emulate neutron radiation at 300 ℃ and 500 ℃. Nano-indentation tests and TEM characterizations were conducted to investigate the hardness variations and irradiation defects, respectively. The results show that irradiations at both temperatures of 300 ℃ and 500 ℃ could cause the increase of hardness. Less hardening is observed in the sample irradiated at 500 ℃ due to effective recombination of irradiation-produced point defects. Sparse dislocation loops are observed in the irradiated layer, which accounts for irradiation hardening. Sparse irradiation-produced dislocation loops are related to the initial microstructure of ODS-Eurofer. Grain boundaries, second phase-matrix interfaces, and dislocations can act as sinks to the point defects during irradiation, which impedes the formation and growth of irradiation dislocation loops.