PurposeAs the solution to improve fatigue life and mechanical reliability of packaging structure, the material selection in PCB stack-up and partitioning design on PCB to eliminate the electromagnetic interference by keeping all circuit functions separate are suggested to be optimized from the mechanical stress point of view.Design/methodology/approachThe present paper investigated the effect of RO4350B and RT5880 printed circuit board (PCB) laminates on fatigue life of the QFN (quad flat no-lead) packaging structure for high-frequency applications. During accelerated thermal cycling between −50 °C and 100 °C, the mismatched coefficients of thermal expansion (CTE) between packaging and PCB materials, initial PCB warping deformation and locally concentrated stress states significantly affected the fatigue life of the packaging structure. The intermetallics layer and mechanical strength of solder joints were examined to ensure the satisfactorily soldering quality prior to the thermal cycling process. The failure mechanism was investigated by the metallographic observations using a scanning electron microscope.FindingsTypical fatigue behavior was revealed by grain coarsening due to cyclic stress, while at critical locations of packaging structures, the crack propagations were confirmed to be accompanied with coarsened grains by dye penetration tests. It is confirmed that the cyclic stress induced fatigue deformation is dominant in the deformation history of both PCB laminates. Due to the greater CTE differences in the RT5880 PCB laminate with those of the packaging materials, the thermally induced strains among different layered materials were more mismatched and led to the initiation and propagation of fatigue cracks in solder joints subjected to more severe stress states.Originality/valueIn addition to the electrical insulation and thermal dissipation, electronic packaging structures play a key role in mechanical connections between IC chips and PCB.