Abstract The irradiation resistance of a reduced activation tungsten-containing high-entropy alloy-based material W0.5(TaTiVCr)0.5 was analyzed using He ions irradiation. Mirror-polished samples were exposed to 200 keV He+ ions at a maximum fluence of 1 × 1021 ions/m2. The nano-indentation hardness of W0.5(TaTiVCr)0.5 increased from 11.6 GPa to 14.9 GPa (at 200 nm depth) following He ion irradiation. Examination of the sample's internal microstructure, using transmission electron microscopy, revealed some randomly dispersed black spots and precursors of He bubbles and dislocations causing irradiation hardening. Relatively better irradiation resistance of W0.5(TaTiVCr)0.5 compared with W, under the given experimental conditions suggests its potential fusion plasma facing applications.