Nano-oxides with low cost are a promising class of reinforcing materials that can be added into solder to enhance reliability of resultant joints. However, the poor interfacial bonding with solder matrix has long been a barrier to its transition from laboratory science to real engineering application. In this study, rare earth Pr and Al2O3 nanoparticles (NPs) were co-added into Sn-0.3Ag-07Cu (SAC0307) solder to solve it, and thermal cycling reliability of resultant joint was found to be much more enhanced when compared to the joints individually added with Pr or Al2O3 NPs. This was attributed to a synergistic effect in-situ built between Pr atoms and Al2O3 NPs, in the form of Pr-coated Al2O3 NPs. This structure helped most Al2O3 NPs maintain nano-scaled during thermal cycling, and thus continuously inhibited the coarsening of interfacial microstructure for a long time. Kinetic analysis showed that the average interfacial IMCs growth coefficient at SAC0307-Pr-Al2O3/Cu interface was about 5.0 × 10−11 cm2/h, lower than that at SAC0307/Cu, SAC0307-Pr/Cu and SAC0307-Al2O3/Cu interface.