The human settlement environment is the object on which human survival depends. In this study, six single factor suitability models and a comprehensive index model of the human settlement natural environment were established. The six single factor models included topography, hydrology, vegetation, soil, temperature and humidity, and land surface temperature. This study took 1 km × 1 km as the pixel size and relied on the ArcGIS platform to systematically and quantitatively evaluate the human settlement environment of the lower reaches of the Yangtze river. The results show that: (1) From the evaluation results of single natural elements, the topography of the study area is relatively flat, with a small number of hydraulic erosion areas. Besides, there are significant differences between the north and the south in temperature and humidity, hydrology, vegetation, and land surface temperature. (2) In 2015, the most suitable areas of human settlement environment were mainly distributed in the plains along the Yangtze river, the plain of northern Zhejiang, and the Poyang plain. The most unsuitable areas are mainly distributed in mountainous areas, such as the mountain area of southern Zhejiang and Dabie mountain area. Topography and vegetation are the dominant factors for classification. (3) From the perspective of space, the score of the human settlement natural environment in Shanghai is above the average, and the best among the other provinces is Jiangsu province, while Zhejiang, Jiangxi, and Anhui provinces have little difference. From the perspective of time, the overall level of the suitability in the lower reaches of the Yangtze river has been improved from 2005 to 2015, mainly due to the influence of temperature and humidity index and water resource index.
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