High 234U/238U activity ratio (AR4/8), identified in groundwater from the Elovka-Kultuk and Nilovka-Mondy inversion sections of the Tunka Valley, coincide with areas of earthquake concentrations. In order to substantiate an approach to earthquake prediction, spatial variations of this parameter were determined in natural water at the western termination of the valley and its temporal variations were monitored in water from the Mon-D well in the Mondy basin in 2013–2017. A recorded gradual decrease of AR4/8 values in water of this well, coeval with preparation and implementation of an earthquake with the energy class K=13.9 in the north of lake Khövsgöl, reflected crack closure that prevented deep water penetration in the Tumelik-Mondy aseismic zone. At the eastern termination of the valley, near the Kultuk village, decreasing AR4/8 values in groundwater were followed with their sharp increasing and transition to low-amplitude variations. Accordingly, crack closing was followed with their opening that facilitated the circulation of deep water and provided seismic events. Leveling of the Mondy anomaly in the Tumelik-Mondy aseismic zone, accompanied by a continuous activity of the Turan and Nilovka anomalies within the Nilovka-Mondy section, emphasized a specific role of the latter as an intermediate chain between the Khövsgöl segment of radial rifts, originated in front of the Hangay orogen, and the largest central basin of the Tunka Valley. The Kultuk, Zaktuy, and North-Tory AR4/8 and earthquake anomalies denoted boundaries of the Elovka-Kultuk section in the Khamardaban lithospheric block flattened at the edge of the Siberian platform basement.