The decentralization processes of the domestic economic system call for finding new approaches to managing the regional economy. One of the most critical tasks is forming effective and efficient mechanisms for ensuring economic security at the regional level, the solution of which, in turn, is a necessary component of the system of economic security at the national level. Therefore, studying the regional aspect of economic security is an urgent task. The essence of economic security at the regional level is considered. Approaches to determining the system of indicators characterizing economic security at the regional level and methods of assessing economic security are analyzed. The practical application of the integral indicator for assessing the economic security of Ukraine’s regions and grouping regions by levels of economic security is considered. The obtained results can be used in developing and revising state and regional development programs in the context of developing measures to ensure the appropriate level of economic security.