The Tian Shan Mountains were formed in the result of the India–Eurasia collision, which leads to creation of contrast high-mountain relief and world known seismic activity. The seismic catastrophes, recorded instrumentally, have occurred to the north of the Issyk-Kul Lake region. There are also known significant earthquakes with magnitude being about 7 in western and eastern parts of the mentioned lake region. Only in the south of the Issyk-Kul depression the strong earthquakes recorded by the seismic network were not known. Our recent study in the south of the Issyk-Kul Lake region has revealed numerous active tectonic structures related to South Issyk-Kul Fault: faults and folds, responsible for strong earthquakes’ occurrence. These were historical and paleoseismic deformations which led to changes in relief: fault scarps and significant rockslides. We have also found spectacular deformations in archeological monuments. All these deformations testify the location of epicentral areas of two strong historic (about 11th and 16th (?) centuries AD) and paleoearthquakes (Holocene and Late Pleistocene). Magnitude of ancient seismic events, according to parameters of the revealed fault scarps, were Ms ≥ 7 and seismic intensity I ≥ IX. All revealed seismic deformations are located to adyrs (piedmonts) of the Terskey Ala-Too range bordered of the Issyk-Kul Lake depression in the south. Their formation is described by the model of a fault which rupture plane becomes shallower southward. This model is complicated by the presence of reverse thrusts. Here, we should admit the existence of a single zone of South Issyk-Kul Fault which is a long-lived feature which separates the structures with the different regime of movements during the Neotectonic time. All obtained data led us to a conclusion of significant underestimation of the seismic hazard in southern Issyk-Kul Lake region.