The buffer-rock barriers system is widely proved to be one of the most promising options for isolating high-level radioactive waste from the human environment. To certify the efficiency and provide the additional development regarding design and assessment of this barriers system, it is essential to understand the complex Thermo-Hydro-Mechanical (THM) behavior of confining buffer under a variety of environmental conditions. To this end, a case of buffer-rock barriers system is studied using a THM finite element approach. The contributions of different processes, including the vapor diffusion process, the water saturation dependent thermal conductivity and specific heat capacity as well as the temperature dependent water properties, involved in the TH couplings are investigated in details. Based on all the simulation results, the key factors of design and assessment of buffer-rock barriers system are also analyzed.