The article discusses the dynamics of mortality in Belgorod Region by major causes revealed on the basis of analysis of the materials of the Territorial Department of the Federal State Statistics Service in Belgorod Region in 2000-2012. According to the analysis, the first three places in the structure of mortality in Belgorod Region are taken by cardiovascular diseases, neoplasms, and external causes of death, accounting 55.4%, 15.3% and 10.2% of deaths in 2012 respectively. The largest contribution to mortality from external causes is made by suicide and transport accidents, accounting 38.6% of all deaths in 2012. The results showed that the mortality rates in men for many reasons are significantly higher than those in females. Particular attention was paid to the causes of death in the population of the working age as a basis for socio-economic potential of the region. It is concluded that the changes in the structure of causes of death were caused as a set of economic, political, medical and social, and environmental factors and their influence under the prevailing conditions of life and features of self-preservation behavior in the region.