Climate change simulation based on 30-member ensemble of Voeikov Main Geophysical Observatory RCM (resolution 25 km) for northern Eurasia is used to drive hydrological model CaMa-Flood. Using this modeling framework, we evaluate the uncertainties in the future projection of the peak river discharge and flood hazard by 2050–2059 relative to 1990–1999 under IPCC RCP8.5 scenario. Large ensemble size, along with reasonably high modeling resolution, allows one to efficiently sample natural climate variability and increase our ability to predict future changes in the hydrological extremes. It has been shown that the annual maximum river discharge can almost double by the mid-XXI century in the outlets of major Siberian rivers. In the western regions, there is a weak signal in the river discharge and flood hazard, hardly discernible above climate variability. Annual maximum flood area is projected to increase across Siberia mostly by 2–5% relative to the baseline period. A contribution of natural climate variability at different temporal scales to the uncertainty of ensemble prediction is discussed. The analysis shows that there expected considerable changes in the extreme river discharge probability at locations of the key hydropower facilities. This suggests that the extensive impact studies are required to develop recommendations for maintaining regional energy security.