In this paper, the thermo-mechanical reliability of IMCs (Ni3Sn4, Cu3Sn, Cu6Sn5) solder joints and Sn-3.9Ag-0.6Cu solder joints were investigated systematically in 3D chip stacking structure subjected to an accelerated thermal cyclic loading based on finite element simulation and Taguchi method. Effects of different control factors, including high temperature, low temperature, dwell time of thermal cyclic loading, and different IMCs on the stress-strain response and fatigue life of solder joints were calculated respectively. The results indicate that maximum stress-strain can be found in the second solder joint on the diagonal of IMC solder joints array, for Sn-3.9Ag-0.6Cu solder joints array the corner solder joints shows the obvious maximum stress-strain, these areas are the crack propagated locations. The stress-strain and fatigue life of solder joints is more sensitive to dwell temperature, especially to high temperature, increasing the high temperature, dwell time, or decreasing the low temperature, can reduce the stress-strain and enlarge the fatigue life of solder joints. The optimal design in the 3D IC structure has the combination of the Cu6Sn5/Cu3Sn, 373K high temperature, 233K low temperature, and 10min dwell time.