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Effect of Cu substrates and solder alloy on the formation of kirkendall voids in the solder joints during thermal aging was investigated. Solder joints with three types of Cu bonding pads (electroplated Cu, polycrystalline Cu and single-crystal Cu) and Sn-based solders (Sn-3Ag-0.5Cu and Sn-37Pb) were prepared, and subsequently the samples were aged at 150°C and 175°C, Under the same aging conditions, it was observed that there were obvious differences in size and distribution of voids inside Cu3Sn for electroplated Cu pad with Sn-3Ag-0.5Cu and Sn-37Pb solders, which is correlated with growth rates of Cu3Sn inside the IMC. The coalescence and combination of kirkendall voids inside Cu3Sn layer mainly occurred in Sn-3Ag-0.5Cu/electroplated Cu system. Also the effect of Cu substrates with different microstructures on the formation of kirkendall voids has been studied. Kirkendall voids were observed only when the electroplated Cu and polycrystalline Cu were used, and was not observed when single-crystal Cu was used. It was proposed that impurities in electroplated Cu helped the nucleation of these voids. We find the tendency for voiding could be correlated with some properties like Cu grain size, crystal defect and purity of Cu material, presumably affected by manufacturing process.