Introduction. A comprehensive assessment of external and internal epidemiologic risks of hosting 2018 FIFA World Cup in the Russian Federation was carried out to improve efficiency of the system of preventive measures. Materials and methods. The work was carried out on the basis of statistical data acquired from WHO, Ministries of Health of the countries, local Rospotrebnadzor offices in host cities of the Russian Federation, and available publications. Results. We analyzed current epidemiologic situation in the countries of the world and assessed risks of importation of each infectious disease by participants and guests to 11 host areas. Internal epidemiological risks were assessed. The assessment made it possible to rank external and internal epidemiologic threats by the extent of potential epidemic hazard and take measures to prevent their importation and spread. Conclusions. We established a high risk of importing cholera, malaria, and dengue fever, a moderate risk of importing measles and chikungunya fever, a low risk of Zika virus disease, and the minimal risk of polio caused by wild-type poliovirus, yellow fever, Middle East respiratory syndrome, plague, Lassa fever, Marburg fever, Ebola virus disease, and avian influenza A (H7N9) during the championship. As for the regional threats, then in the Republics of Tatarstan and Mordovia, Nizhny Novgorod and Samara Regions the most significant was hemorrhagic fever with renal syndrome while in the Sverdlovsk Region, Moscow, and St. Petersburg lime borreliosis posed the highest risk. The moderate risk of tick-borne encephalitis was determined in the Sverdlovsk Region, of Crimean hemorrhagic fever – in the Rostov Region, and that of West Nile fever – in the Volgograd Region. Differentiation and ranking of epidemiologic risks by the extent of potential epidemic hazard allowed us to substantiate the main organizational, preventive, and anti-epidemic measures during 2018 FIFA World Cup and ensure sanitary and epidemiologic well-being of the population.