The relevance of the study is determined by the need to develop a methodology for analyzing regional development to identify the challenges of the pandemic, as well as the search for effective tools to ensure the economic security of Russian regions, taking into account real and expected threats. The purpose of the article is to identify the challenges of the COVID-19 pandemic for the economic security of Russian regions, as well as to substantiate a set of effective measures to overcome emerging problems of regional development. The objectives of the study are: to determine the features of the COVID-19 pandemic and its impact on the socio-economic development of regions; systematization of the pandemic's challenges for the economic security of Russian regions; development of a mechanism to ensure the economic security of Russian regions during the pandemic. The methodology of the research is based on the use of the method of systematization, the method of economic and statistical analysis, the method of comparative analysis, the method of induction and deduction, the graphical method, as well as a systematic approach to achieve the goals and objectives. Results. As a result of the conducted research, the features of the COVID-19 pandemic and its impact on the socio-economic development of the regions of Russia are determined. The authors propose a system of indicators adapted to analyze regional development and identify pandemic challenges for regions, in particular, by introducing indicators of the sanitary and epidemiological situation. The analysis of the state of regional economic systems during the pandemic allowed the authors to identify the real and expected challenges of the pandemic for the economic security of Russian regions. Conslusions. The article proposes measures of state policy to ensure the economic security of Russian regions, taking into account the real and expected challenges of the pandemic. The obtained results develop the theoretical foundations of the study of the problems of economic security of regions, and can also be used in the practical activities of regional authorities as a methodological basis for the formation of tools for leveling threats to economic security.