Abstract With the development of packaging devices toward high performance and high density, electronic devices are subjected to thermo-electric stresses under service conditions, which has become a particularly important reliability problem in micro-electronics packaging. The reliability of the chip under thermo-electric stresses is studied in this paper. First, thermo-electric coupling experiments were carried out on two solder joint structures of Ni/Sn3.5Ag/Cu and Ni/Sn3.5Ag/Ni. The interface evolution of solder joints under different current densities was analyzed. The reliability of the two structures under thermo-electric stresses was compared and analyzed. After that, three-dimensional finite element analysis was employed to simulate the current density, Joule heat, and temperature distribution of the flip chip. Finally, through the combination of experiment and simulation, the distribution of Joule heat and temperature of the chip was analyzed. The results show that the Ni/Sn3.5Ag/Ni structure has better reliability than the Ni/Sn3.5Ag/Cu structure under thermal–electric coupling. In addition, when the Ni layer was used as the cathode side, the constant temperature applied on the chip was 150 °C, and the current density was higher than 5 × 104 A/cm2, the dissolution failure of the Ni layer occurred in two structures. Because the higher current density generated a large amount of Joule heat where the current was crowded, resulting in excessively high temperature and rapid dissolution of the Ni barrier layer.