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A physically-based semi-distributed hydrological model ECOMAG was applied within the ISI-MIP framework for assessing climate change impact on water regime of the Lena River basin (the catchment area is 2 488 000 km2). The model describes processes of snow accumulation and melting, soil freezing and thawing, water infiltration into unfrozen and frozen soil, evapotranspiration, thermal and water regime of soil under the influence of permafrost, overland, subsurface and channel flow. Most of the model parameters were assigned from the global and regional datasets. Calibration and validation of the model were carried out against the available long-term streamflow records at the Stolb and Krestovsky gauges. The calibration was made in two steps: firstly using meteorological observation data, and then re-calibrating to reanalysis data. Four reanalysis datasets provided by the project organizers were used for historical runs. The calibration and validation sub-periods were of 10 years (2000-2009) and 14 years (1986-1999), respectively. The model was evaluated through its ability to reproduce daily streamflow hydrograph and hydrological extreme characteristics for multi-year period and demonstrated good performance, when using both observational and the bias-corrected reanalysis data. Opportunities of the ECOMAG model application for deriving hydrological projections from the climate model outputs were investigated with emphasis on the projection uncertainty issues. An approach was proposed for assessing internal atmospheric variability effect on the ECOMAG-based simulation uncertainty. The internal atmospheric variability was reproduced through ensemble climate model experiment and considered as the lowest level of uncertainty achievable in climate impact studies.