Abstract: Vanadium alloys (V-5Cr-5Ti) have been considered as the candidate materials for the first wall and the blanket of fusion reactors. Different fabrication process will affect the performance of vanadium alloy in fusion reactors. In this study, the response of hardening of V-5Cr-5Ti vanadium alloys with different cold deformation (40%, 60% and 80%) followed by annealing treatment (1 273 K for 1 h) under irradiation with 337 MeV Fe ions was investigated. The irradiation experiment was performed at a terminal of the Sector-Focused Cyclotron(SFC) at HIRFL(Heavy Ion Research Facility in Lanzhou). The results of electron backscattering diffraction(EBSD) indicated that the proportion of fine broken grains in the sample increased and the average grain size decreased with the increase of cold deformation amount. After annealing, the distribution of grains become more uniform with the fine broken grains growing up and the large grains almost disappeared. The results of the Vickers hardness test show that the hardness increases with the increase of cold deformation amount and decreases after annealing treatment. After irradiation, the hardness of all samples increased significantly, which suggested the occurrence of irradiation hardening. In both cold rolling samples and annealing samples, the irradiation hardening effect decreased with the increase of cold deformation amount, which indicated that cold rolling can significantly improve the irradiation hardening resistance property. Based on the EBSD and hardness results, the mechanism of the effect of cold rolling and annealing on irradiation hardening resistance property of V-5Cr-5Ti was discussed. The increase of the cold deformation amount results in the increase of the sink strength, which suppressed the occurrence of irradiation hardening. The annealing treatment results in the decrease of the density of grain boundary and dislocation and the decrease of the total sink strength, which caused more significant irradiation hardening in the sample with annealing treatment.