The enhancement of helium ion (He+) radiation tolerance and mechanical behavior of high entropy alloys (HEAs) have triggered significant research interest. In this work, the ultra-fine nano-crystalline Al1.5CoCrFeNi HEA films with single phase structure were prepared, which were irradiated at 300 K with 60 keV He+ in a wide fluence ranging from 1 × 1016 cm−2 to 1 × 1017 cm−2. The effects of ultra-fine nano-crystalline on He evolution behavior, radiation tolerance and mechanical behavior in Al1.5CoCrFeNi HEA films were investigated. The results show that the He clusters preferentially distributed along the grain boundaries (GBs) rather than in grains due to the defect sink effect of nano-GBs. No observable He bubbles were observed in the peak damage region of the films even though the He concentration is up to 8.50 at.% at the fluence of 1 × 1017 cm−2. Some grains with limited irradiation damage keep their stability and integrity by eliminating the irradiated defects at GBs, exhibiting enhanced radiation tolerance in the ultra-fine nano-crystalline HEA film. The dependence of phase stability on the suppression of radiation-induced segregation level owing to the design of ultra-fine nano-crystalline and high lattice distortion was revealed in detail. Moreover, the ultra-fine nano-crystalline HEA films display higher swelling resistance than that of bulk coarse-grained HEA materials by reducing the size of He clusters. Higher relative hardness(H/H0) was observed in the irradiated ultra-fine nano-crystalline HEA film compared to that of the bulk coarse-grained HEA, Finally the relevant hardening mechanisms were also discussed.