We examined the interfacial reactions between Sn–3.0Ag–0.5Cu (SAC305) alloy/FeCoNiMn (FCNM) high-entropy alloy (HEA) and Sn–58Bi (SB58)/FCNM. FCNM exhibits a single phase with Fe, Co, Ni, and Mn solid solutions, and the FCC phase has a lattice constant of 3.601 Å, as determined by X-ray diffraction. Further, SAC305 and SB58 exhibit slightly better contact angles and spread rates on FCNM than that on Cu, which is consistent with their interfacial energies calculated by density functional theory simulations. Additionally, there is an extremely thin interlayer between SB58/FCNM (0.128 μm thickness), which is a multi-element intermetallic compound with 13.42%, 7.89%, 5.26%, 5.79%, and 67.63% (at.%) of Fe, Co, Ni, Mn, and Sn, respectively, expressed by the (Fe, Co, Ni, Mn)Sn2 intermetallic compound. The dissolution rate of FCNM into Sn was very low during the reflow process of 20 min. The findings indicate that FCNM is a promising material as a diffusion barrier between Sn-based solder/Cu solder joints with a small solder volume in a three-dimensional integrated circuit.