[Purposes] The permeability of reservoir rocks is usually anisotropically distributed, and it is necessary to explore its impact on the seasonal operating performance of compressed air energy storage in aquifers (CAESA) systems. [Methods] By establishing the conceptual model of the CAESA system and the 3D well group-reservoir numerical grid, three reservoir permeability anisotropic distribution cases were set. Then, the fluid mass transfer and heat transfer processes of the CAESA system under seasonal cycle operating mode and permeability anisotropic distribution conditions were particularly studied by using the numerical simulation program T2WELL/EOS3. [Findings] The permeability anisotropy of the reservoir affects the gas phase migration, fluid interaction, temperature and pressure transfer process in the wellbore-reservoir, and then affects the energy storage efficiency of the system. The ratio of transverse permeability to longitudinal permeability increases from 2.0 to 10.0. The maximum pressure of the wellbore decreased by 2.79 MPa, and the maximum temperature of the wellhead during the production stage increased by 2.06 °C. The occurrence time of two-phase flow at the wellhead has been advanced from the 435th day of system operation to the 410th day, and the system energy storage efficiency decreased from 89.8% to 60.1%. [Conclusions] For reservoirs with high permeability anisotropy, the system support pressure can be increased by increasing the initial airbag injection volume or supplementing air in the later stage, or by using engineering methods such as grouting modification and establishing artificial low-permeability boundaries to optimize reservoir conditions and improve system energy storage efficiency.