The article presents the comprehensive analysis results of the connection between structural changes caused by the effects of deformation swelling and softening effects during high-dose irradiation with He2+ ions, alongside determines the kinetics of changes in structural and strength parameters contingent upon irradiation conditions (in the case of irradiation temperature variations). The interest in such studies is due to the need to study the influence of temperature factors on the diffusion mechanisms of implanted He2+ into the damaged layer of a high-entropy TiTaNbV alloy in the case of high-dose irradiation. At the same time, the study of such mechanisms makes it possible to determine not only the radiation resistance of TiTaNbV alloys, but also to expand the general understanding of the influence of the structural features of high-entropy alloys associated with deformation distortion of the crystal structure, which prevents diffusion and migration mechanisms of defect propagation in the damaged layer. During determination of changes in strength properties depending on irradiation conditions, it was found that irradiation temperature growth leads to both a rise in the degree of softening under high-dose irradiation and an increase in the thickness of the softened layer under high-dose irradiation. These changes indicate that at high temperatures, the diffusion of implanted ions is not restrained by structural distortions, which results in their migration to a greater depth exceeding the ion travel depth, which should be considered when designing the use of these alloys in the case of their operation in extreme conditions.