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CoCrFeCuNi high-entropy alloys (HEAs) prepared by arc melting were irradiated with a 100 keV He⁺ ion beam. Volume swelling and hardening induced by irradiation were evaluated. When the dose reached 5.0 &#215; 10¹⁷ ions/cm², the Cu-rich phases exhibited more severe volume swelling compared with the matrix phases. This result indicated that the Cu-rich phases were favorable sites for the nucleation and gathering of He bubbles. X-ray diffraction indicated that all diffraction peak intensities decreased regularly. This reduction suggested loosening of the irradiated layer, thereby reducing crystallinity, under He⁺ ion irradiation. The Nix-Gao model was used to fit the measured hardness in order to obtain a hardness value <i>H</i>₀ that excludes the indentation size effect. At ion doses of 2.5 &#215; 10¹⁷ ions/cm² and 5.0 &#215; 10¹⁷ ions/cm², the HEAs showed obvious hardening, which could be attributed to the formation of large amounts of irradiation defects. At the ion dose of 1.0 &#215; 10¹⁸ ions/cm², hardening was reduced, owing to the exfoliation of the original irradiation layer, combined with recovery induced by long-term thermal spike. This study is important to explore the potential uses of HEAs under extreme irradiation conditions.