The comprehensive suitability of regional human settlements is of great significance to the development and spatial distribution of regional human settlements and regional social and economic development. In this study, based on the traditional evaluation of the natural suitability of the human settlements, this study adds humanistic indicators to comprehensively evaluate the suitability of the human settlements in Liaoning, China. In particular, we sought to uncover the spatial differentiation law of the comprehensive suitability of these settlements and its correlations with population density and GDP density, provide a theoretical basis for urban human settlements planning and governance. The main conclusions were as follows: (1) the natural suitability index in Liaoning Province presents the law of longitudinal spatial differentiation from northeast to southwest, which follows the direction of the mountains; (2) the highest to lowest humanistic suitability indexes were as follows: the central, eastern, and western regions; (3) the highest to lowest spatial differentiations of the comprehensive suitability of the human settlements were as follows: the central and coastal, eastern, and western regions;(4) the spatial distribution of population–economy density in Liaoning Province was basically consistent with the spatial distribution of the comprehensive suitability index of human settlements, The population economy is concentrated in the areas with the best and moderate human settlements. Ultimately, we found that the distributions of population–economy and human settlement suitability were relatively coordinated and that highly suitable land was already fully utilized.