The active layer in permafrost region is inevitably subjected to seasonal freezing-thawing actions. The soil freezing and thawing can change boundary conditions of the bridge pile foundation in permafrost region, which will influence the seismic responses of the bridge. In this study, to investigate the influence of seasonal freezing-thawing soils on seismic performance of high-rise cap pile foundation in permafrost region, quasi-static tests were carried out on two 1/8 scaled models. The hysteretic behaviors and damage characteristics of the pier-pile-soil system in permafrost region with thawed and frozen active layer were analyzed. It is found that the freezing-thawing status of the active layer can relocate the vulnerable position of the pile foundation in permafrost region. Furthermore, the frozen active layer limited the deformation capacity of the pier-pile-soil system, then resulted in the redistribution of the pile stress. Although the frozen active layer in winter season enhanced the bearing capacity of the pier-pile-soil system, it weakened the ductility of the pier-pile-soil system. Additionally, the frozen soil temperature and the shear strength of the active layers will affect the adhesive force of the permafrost layer. These results can provide a scientific basis for the seismic design of bridges with pile foundation in permafrost regions.