The issue of improving the quality of life of the population of Russian regions is relevant for a number of reasons: the need to achieve a decent standard of living of the population, comparable to the level of developed countries and leading regions of the Russian Federation; taking into account the peculiarities of regional development; objective restrictions in people’s lives caused by crisis development factors, including epidemic waves, sanctions pressure from unfriendly countries, etc. For operational management influence, a tool is needed that would ensure constant monitoring of the quality of life of the population, the level and dynamics of its changes. However, today, existing methods for assessing the quality of life are a labor-intensive and time-consuming scientific task with a large number of indicators. The purpose of this study is to substantiate environmental and economic security as a predictor of the quality of life of the population of the region and to develop an express method for assessing the level of its provision. In the work, the authors used such methods as analysis and synthesis of scientific information, an index method for assessing the key components of the environmental and economic security of the region based on subindices. The results of the study substantiate the essence of the ecological and economic security of the region as a predictor of the quality of life of the population, which is the ability of the regional ecological and economic system to maintain its current state and the possibility of development under the influence of external or internal influences, including man-made ones, and also to function without changing its own structure and be in balance to ensure the normal functioning of the population of the region. Based on the index method for assessing the key components of the region’s environmental and economic security, the values for three subindices (sustainability, stability and technogenicity) were determined, as well as the integral index of environmental and economic security of the regions of the Ural Federal District, which were divided into two groups for correct comparison, from 2017 to 2021, the leading regions were identified (Yamalo-Nenets Autonomous Okrug, II (2021) = 0.743; Kurgan region, II (2021) = 0.508) and outsider regions (Khanty-Mansiysk Autonomous Okrug — Yugra, II (2021) = 0.475; Sverdlovsk Region, II (2021) = 0.391).