An attractive approach to mitigate hydrogen embrittlement (HE) is to use nano-sized particles to immobilize hydrogen. However, the atomic scale relationship between different particle-matrix characteristics in aluminum alloys and the susceptibility to HE is unknown. In this study, the effects of interactions between various interfaces and hydrogen in aluminum alloys are investigated using a comprehensive multiscale experimental and simulation-based approach that includes atomic-scale observations, simulation and advanced hydrogen mapping techniques. Depending on the nature of interfaces, e.g., coherency, size, and crystal structure, some are useful for mitigating HE, others provide hydrogen to sensitive sites, and some act as crack initiation sites.