This study investigates the interfacial reaction between powder-metallurgy high-entropy alloys (HEAs) and cast aluminum. HEA pellets are produced by the spark plasma sintering of Al_0.5CoCrCu_0.5FeNi HEA powder. These sintered pellets are then placed in molten Al, and the phases formed at the interface between the HEA pellets and cast Al are analyzed. First, Kirkendall voids are observed due to the difference in the diffusion rates between the liquid Al and solid HEA phases. In addition, although Co, Fe, and Ni atoms, which have low mixing enthalpies with Al, diffuse toward Al, Cu atoms, which have a high mixing enthalpy with Al, tend to form Al–Cu intermetallic compounds. These results provide guidelines for designing Al matrix composites containing high-entropy phases.