The Liskin fault zone located in the southeastern part of The East European Platform on the border of two large neotectonic structures — the Voronezh Uplift and the Oka-Don basin is considered. A concentration of earthquake epicenters is confined to the fault zone and the adjacent territory. The neotectonic structures of the territory, relief, structure of the multi-depth and age horizons of the sedimentary cover, basement, crust, Moho surface are investigated, and the causes of neotectonic and seismic activity of the zone are determined. The Liskin fault at the present time developing as a thrust with right component under the conditions of submeridional compression and the adjacent territory is under the influence of multidirectional tectonic compression stresses: from the north, from the Oka-Don basin and from the south, from the Caucasian segment of the Alpine collision belt. This is reflected in the morphology and structure of the newest structures. The deformation of multi-depth horizons as well as the Earth’s surface and the activating of seismicity are associated with the submeridional compression. The deep material and structural inhomogeneities of the Earth crust are of great importance. For the first time in the newest structure of the south-eastern part of the East European Platform, the collision area of two oncoming submeridional stresses that caused active seismicity has been identified.