• Grain orientation has a crucial effect on the fatigue mode of Sn-rich solder joints. • A new failure mode of Sn-rich solder joints in SiP was found. • Traditional fatigue life prediction model for Sn-rich solder joints is questionable. In this paper, a thermomechanical anisotropic constitutive model was employed to investigate the failure mode of multiple Sn-rich solder joints in system in package under thermal cycle loading. As a comparison, traditional isotropic constitutive model was also employed to investigate the failure mode. Results showed that the anisotropic constitutive model predicted a new failure mode that failure would occur earlier at inner solder joint rather than the outmost solder joint, which was different from traditional perspective. This new failure mode indicated that traditional fatigue life prediction model just based on the outermost solder joint was not enough in view of the thermomechanical anisotropic performance of Sn-rich solder.