Multi-stage desiccant wheel systems are an effective way to increase the performance of desiccant dehumidification. In this paper, a heat pumpdriventwo-stage desiccant wheel (HPTW) system is proposed. Between two adjacent desiccant wheels, an evaporator is inserted at the processed airside to provide cooling capacity for dehumidification, and a condenser is inserted at the regeneration air side to provide heat capacity for regeneration.A low regeneration temperature under 50oC(122oF) can be realized, and the system COP is higher than 4, which is better than traditionalcondensation dehumidification methods or single-stage desiccant wheel systems; the lower the humidity ratio of the processed outdoor air, the higherthe COP of the two-stage desiccant wheel system. The proposed HPTW system can be applied in office buildings for dehumidification to realizetemperature and humidity independent control, and a high evaporating temperature chiller (HEC) can be used to deal with the sensible heat load.The performance of the HPTW and HEC system is simulated in a typical office building in Beijing and Guangzhou. The hour-by-hour sensibleand latent loads of the building are calculated using DeST software. The annual energy consumption of the HPTW and HEC system isanalyzed and compared with that of a traditional HVAC system using a low evaporating temperature chiller (LEC). The results show that theenergy-saving potential of the proposed system is around 15-35% compared to the conventional system.