The air-conditioning system of office building is a large power consumption terminal equipment, whose unreasonable operation mode leads to low energy efficiency. Realizing the optimization of the air-conditioning system has become one of the important research contents of the electric power demand response. To reduce electric bill and improve energy efficiency of the air-conditioning system, two-layer flexible optimal strategy for air-conditioning of office building under TOU price is put forward. In the upper level, the operation mode of the air-conditioning system is optimized in order to minimize the uses' electric bill and ensure user' comfort according to the information of outdoor temperature and TOU price, and the cooling load of the air-conditioning is output to the lower level model. In the lower level, the distribution mode of load among the multi water chillers is optimized in order to maximize the power efficiency according to the characteristics of each chiller. The PSO algorithm is employed to solve the two-layer optimization model. The experimental results under different modes of air-conditioning show that the strategy can improve the efficiency of chillers and save the electric bill. This work is supported by National Natural Science Foundation of China (No. 51577051).