Abstract: In this paper, Sn and Sn3.9Ag0.6Cu solders, which are widely used in industry, were selected as bonding materials for 3D packaging chips. The 3D packaging model was established using ANSYS finite element software. Based on the Garofalo-Arminius’s constitutive equation, the process of thermal cycle under the temperature condition from −55 ~ 125 °C. In addition, the influence of packaging structure and process parameters on the reliability of solder joint was discussed by Taguchi method. The results show that the contact area between Cu pillar and solder joint is the weak area of the whole structure, and the maximum stress appears at the second solder joint in the rightmost row of the intermetallic compound (IMC) solder joint array. Through the Taguchi method and combined with the finite element simulation results, the contribution of the four factors to S/N was obtained as follows: solder joint array, solder joint height, chip thickness, solder joint material, of which the solder joint array has the largest influence, followed by solder joint height and chip thickness, solder joint material has the least influence. Based on the optimization design, the optimal matching combination was solder joint array 3 × 3, solder joint height 0.02 mm, chip thickness 0.2 mm and solder joint material Cu₆Sn₅.