Assessing the energy saving of natural ventilation is difficult, especially for large scale naturally ventilated buildings, due to the lack of deterministic data and method. This paper presents a method, integrating simulation by both software of DeST-h and computational fluid dynamics (CFD) in typical meteorological year (TMY) in Guangzhou, to evaluate quantitatively the natural ventilation cooling effect. The results showed that the cooling effect of natural ventilation was influenced by the windows and doors switching. Air conditioning operating hours reduction in the living room can reach 509h by natural ventilation during the occupied time with the windows and doors opened, which can reach 325h with the windows opened and doors closed. The cooling effect of natural ventilation was more significant in windows and doors opened case than that in windows opened and doors closed case. Annual rate of cooling loads reduction in rooms and building were 0.34~10.50% and 6.14% respectively. It is necessary to organize and design building opening to maximize the natural ventilation using.