Vanadium alloys have been regarded as the promising candidate structure materials for the advanced blanket concept in fusion reactor due to the low activation, good high-temperature strength and especially the compatibility with liquid lithium. In the present work, six kinds of V-5Cr-5Ti alloys under heavily cold work with deformation amounts of 40%, 60% and 80%, and/or subsequent annealing were investigated. Irradiation damage of 0.1, 0.3 and 0.5 dpa was introduced in both specimens by using 352.8 MeV Fe ions at 100 ℃. Electron backscattered diffraction (EBSD) and transmission electron microscopy (TEM) were used to investigate pre-irradiation microstructures such as grains, dislocations, precipitates, and bubbles. XRD was used to evaluate the pre-existing dislocation density and TEM was used to image irradiation defects. Change in hardness was evaluated by using micro-hardness tests. Before irradiation, hardness increased with increasing deformation amount but decreased after subsequent annealing. Dislocation cells turning into sub-grains with low-angle boundaries was observed while deformation amount reaching 80% in cold-worked specimens. After irradiation, hardening was observed in all specimens and doses, and a power-law relation was observed in dose dependent hardening. Effect of initial microstructure on irradiation hardening was discussed in terms of sink strength while ignoring grains and precipitates due to their large size. Pre-existing bubbles could effectively reduce irradiation hardening while compared with previous papers. Meanwhile, with increasing sink strength of dislocations, hardening decreased in a different manner in cold-worked and annealed specimens. Irradiation defects in some specimens were investigated to clarify the inherent mechanism in the relation between initial microstructures and irradiation hardening.