Xinjiang Province, China is recognized for the longevity of its inhabitants. To study the temporal and spatial variation of longevity region and chemical characteristics of natural water of longevity region in Xinjiang, three population censuses on county-level and 51 natural water samples from Hotan Prefecture, Xinjiang were collected and analyzed. 103 natural water samples were collected from the public papers. Population statistics on county-level showed that the number of centenarians per 100,000 inhabitants (OC) in Southern Xinjiang was 7.4(year 1990), 4.9(year 2000) and 2.1 times (year 2010) more than that of Northern Xinjiang, respectively. And distribution of the longevity index (LI%), centenarity index (CI%) and number of centenarians per 10,000 over 65 year-old subjects (UC) on county-level decreased from south to north. Natural water in Northern Xinjiang was mainly fresh soft water, and it was mainly fresh hard water and brackish hard water in Southern Xinjiang. Water quality of natural water in Northern Xinjiang was superior compare to that of Southern Xinjiang, while number of centenarians 65 year-old & over per 10,000 subjects in Northern Xinjiang were less than that of Southern Xinjiang before 2010. The research indicates that keeping on drinking water with high total hardness (TH) and Mg/Ca ratio might be good for the health.