V₂AlC coatings prepared by magnetron sputtering on a Zr substrates were irradiated with He ions to simulate the behavior of accident tolerant fuels (ATFs) in a reactor. TEM analysis and scratch test showed that the He bubbles preferentially nucleated along the substrate-coating interface and resulted in a loss of mechanical resistance of the V₂AlC coating (i.e., reduced the adhesion of coating). This study provides a first insight into the irradiation-induced mechanical behavior of V₂AlC coating on the Zr substrate and demonstrates the importance of improving the irradiation resistance of the cladding-coating system by optimizing the interfacial structure between the cladding and the coating materials for the development of ATFs.