FeCrAl alloys are regarded as highly promising candidates for accident-tolerant fuel cladding. This study investigates the influence of hot isostatic pressing (HIP) on the microstructural evolution and mechanical properties of additively manufactured FeCrAl alloys subjected to He ion irradiation. Irradiation experiments were conducted on both the as-printed and HIP-treated conditions of additively manufactured FeCrAl alloys at 350 °C and 450 °C, using 400 keV He ions with a fluence of 1.02 × 101? ions/cm2. The formation and evolution of irradiation-induced defects, including He bubbles and dislocation loops, as well as the corresponding changes in mechanical properties, were systematically characterized and analyzed using transmission electron microscopy (TEM) and nanoindentation techniques. The results indicate that, following HIP treatment, the size of dislocation loops and He bubbles in FeCrAl alloys increased, while the density of He bubbles decreased, compared to the pristine as-printed state. Nanoindentation measurements further revealed that the irradiation hardening rate of the HIP-treated FeCrAl alloy (52%) is significantly higher than that of the as-printed alloy (41%) under identical irradiation conditions. The DBH model calculations confirmed that He bubbles and dislocation loops in the irradiated samples are the primary contributors to irradiation-induced hardening. The analysis suggests that the high density of dislocation lines in the as-printed state facilitates the effective absorption of He atoms and interstitials, which in turn reduces the density and size of dislocation loops and suppresses the growth of He bubbles. The microstructural modifications induced by HIP have been found to reduce the irradiation resistance of the additively manufactured FeCrAl alloys to some extent. HIP is commonly used to enhance the mechanical properties of additively manufactured alloys. However, this process eliminates pre-existing point defect sinks in the alloy, which, to some extent, reduces the material's irradiation resistance.