Natural ventilation is the most effective measure to reduce the cooling energy consumption, but it is quite difficult to control and quantitatively assess the natural ventilation. A method was developed with coupling simulation by both software of DeST-h and computational fluid dynamics (CFD) in typical meteorological year (TMY) in Guangzhou. First, the base room temperatures with different air change (ACH) rates of natural ventilated dwelling were simulated with DeST-h. The time period in that the indoor air temperature could meet thermal comfort requirement only by natural ventilation in occupied period was analyzed, in which the wind speed and direction in TMY was obtained for the ventilation environment simulation of rooms in windows and doors switching with the PHOENICS software. The actual air change rates in different rooms in such wind speed and direction were calculated. Also the cooling loads of building in the actual air change rates were simulated with intermittent air conditioning. The air conditioning system operated when the base room temperature was higher than 29°C. Rate of cooling loads reduction was calculated by comparing the result to the baseline, which were the cooling loads of building with 1 ACH. The actual air change rates show that the energy saving effect of natural ventilation was influenced by the windows and doors switching. 61~71.37% of the natural ventilation potential was used in the rooms with windows and doors opened, and 14.06~82.54% of the natural ventilation potential was used in the rooms with windows opened and doors closed. The rate of cooling loads reduction in rooms and building were 0.34~10.50% and 6.14% respectively.