The article considers the structural changes in the party system of the Slovak Republic, taking place in 2016– 2020 due to the strengthening of parties of anti-systemic populist orientation. The author researches the causes and factors of evolution of the party landscape in the EU countries towards institutionalisation of antisystem policy. The development of the Slovak party system reflects the key trends in the political development of the EU countries with the weakening position of the systemic party establishment and the strengthening role of populist parties. The complexity of the phenomenon of antisystemicism in modern conditions is emphasized, since mainstream parties, seeking electoral support, use the rhetoric of populist parties, and populist parties, haveing obtained parliamentary mandates, weaken their radicalism and start working in the mainstream format. As a result of the 2016 parliamentary elections, the breakdown of the “structural nucleus” of Slovakia’s party system took place, which for two decades had been the basis of its stability and predictability of development. The weakening influence of “traditional” (Christian-Democratic, Conservative, Social-Democratic) parties freed up electoral environment for “new” populist, anti-systemic, right-wing extremist forces. Electoral statistics demonstrates that the influence of mainstream parties weakens at the regional and local levels of Slovak politics. The results of the 2020 parliamentary elections demonstrate that the party system of Slovakia in the continuum between mainstream and populism comes even closer to the populist format. The electoral triumph of populists and their convergence with programmatic parties within the parliamentary-governmental coalition raises new challenges for Slovakia’s political system. Among the main reasons for the rise of populism in Slovakia are the following: disappointment of citizens with the activities of the ruling elites; mediation and personalisation of policy; denationalisation of politics and increasing importance of global governance structures at European and world levels; increasing populism in Slovakian election campaigns; low level of institutionalisation of political parties and the party system as a whole. Attention is drawn to the destructive tendencies in the development of the modern party system of Slovakia. The collapse of the “structural core” of the Slovak party system and the further pluralisation of parliamentary representation of parties do not contribute to the stability and predictability of parliamentary-governmental activity. Increased electoral influence and parliamentary representation of political subjects of populist, anti-systemic and right-wing extremist orientation cause political risks for the stable democratic development of the Slovak Republic.