Natural cooling is one of the more energy-efficient and widely used cooling methods in data center air conditioning systems. Based on the climatic characteristics of Suzhou, Beijing, Guiyang, Guangzhou and Urumqi, the natural cooling system model of data centers was established by TRNSYS, and then the energy saving effect of data centers under the same chilled water supply and return temperatures in different regions was studied. The results show that when the chilled water supply/return temperatures are 15/22℃, the longest time for complete natural cooling is in Urumqi, accounting for 67.4% of the year, and the shortest time is in Guangzhou, accounting for 10.2% of the year; the longest time for complete mechanical cooling is in Guangzhou, accounting for 63.0% of the year, and the shortest time is in Urumqi, accounting for 4.3% of the year; the longest time for part of natural cooling is in Guiyang, accounting for 31.8% of the year, and the shortest time is in Beijing, accounting for 4.3% of the year. The longest part of natural cooling time is in Guiyang, accounting for 31.8% of the year, and the shortest is in Beijing, accounting for 18.6% of the year. At full load, the lowest annual average system power usage effectiveness (PUE) was in Urumqi at 1.227, and the highest PUE was in Guangzhou at 1.299. The average annual PUE of the five cities decreases as the load factor increases, and the effect of air conditioning load on the average annual PUE becomes smaller as the load factor increases. The findings provide theoretical support for guiding the application of natural cooling technology in data centers in different regions.