A series of high-entropy alloys (HEAs) containing nanoprecipitates of varying sizes were successfully prepared by a non-consuming vacuum arc melting method. In order to study the irradiation evolution of helium bubbles in the FeCoNiCr-based HEAs with γ' precipitates, samples were irradiated with 100 keV helium ions to a fluence of 5 × 1020 ions/m2 at 293 K and 673 K. And the room temperature irradiated samples were annealed at different temperatures to examine the diffusion behavior of helium bubbles. Transmission electron microscope (TEM) was employed to characterize the structural morphology of precipitated nanoparticles and the evolution of helium bubbles. Experimental results reveal that nanosized, spherical, dispersed, coherent and ordered L12-type Ni3Ti γ' precipitations were introduced in FeCoNiCr(Ni3Ti)0.1 HEAs by means of ageing treatments at temperatures between 1073-1123 K. Under the ageing treatment conditions applied in this work, γ' nanoparticles were precipitated in FeCoNiCr(Ni3Ti)0.1 HEAs with average diameters of 15.80 nm, 37.00 nm and 62.50 nm, respectively. The average sizes of helium bubbles observed in samples after 673 K irradiation were 1.46 nm, 1.65 nm and 1.58 nm, respectively. The improvement in the irradiation resistance of FeCoNiCr(Ni3Ti)0.1 HEAs was evidenced by the diminution in bubbles size. Furthermore, FeCoNiCr(Ni3Ti)0.1 HEAs containing γ' precipitates of 15.8 nm exhibited the minimum size and density of He bubbles, which can be ascribed to the considerable helium trapping effects of heterogeneous coherent phase boundaries. Subsequently, annealing experiments conducted after 293 K irradiation indicate that HEAs containing precipitated phases exhibit smaller apparent activation energies (Ea) for helium bubbles, resulting in larger helium bubble sizes. This study provides guidance on improving the irradiation resistance of L12-strengthened high-entropy alloys.