A CoCrFeNiNb0.65 eutectic high-entropy alloys (EHEAs) prepared by arc melting were irradiated with a 100 keV He+ ion beam. Swelling, helium bubbles and mechanical response induced by irradiation were evaluated. When the ion fluence reached 1.0×1018 ions/cm2, the irradiation-induced swelling occurred on the sample surface, and as the ion fluence increasing, the swelling became increasingly severe and the surface of Nb-rich phase appeared peeling and shedding. Meanwhile, along the boundaries of matrix and Nb-rich phase there was a neat line of helium bubbles. The size of these helium bubbles decreased with distance from the center of the helium bubble layer. This result indicated that the phase boundaries were favorable sites for the nucleation and gathering of helium bubbles. Nanoindentaion results indicated that hardening and softening induced by He+ ion irradiation occurred in various ion fluences. At ion fluence of 5.0×1017 ions/cm2, the CoCrFeNiNb0.65 EHEAs exhibited an obvious hardening behavior, which can be explained by dislocation-dominated hardening effect. When the ion fluence reached 1.0×1018 ions/cm2 and 2.0×1018 ions/cm2, the hardening effect decreased probably due to the helium bubble aggregation and growth, as well as helium bubbles induced noncompact structures. The results of this study provide insights into the effect of helium bubbles on mechanical evolution and pave the way for designing EHEAs suitable for the nuclear industry.