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This paper presents a validation of outputs from some GCMs of the CMIP6 project when used to assess climate projection and hydrological flows at a catchment scale for the case study area of the Lombardy region (Northern Italy). The modeling chain consists of (i) a choice of climatic scenarios from 10 GCMs of the CMIP6, (ii) the application of a stochastic downscaling procedure to make projections usable at the local scale, and (iii) the use of a semi-distributed physically based hydrological model Poli-Hydro for the generation of hydrological scenarios. Data on observed precipitation and temperature were collected from automatic weather stations, and the hydrological budget of four target catchments within the study area was assessed using Poli-Hydro. An ex-post (back-casting) analysis was performed upon the control data series from the GCMs by comparing statistics of relevant climate variables and model-simulated discharges against observed counterparts during the historical period 2002–2014. Then, during 2015–2021, the goodness of projections was assessed using confidence intervals. Our results show that the accuracy of GCMs in representing regional climate is not always reflected in a credible evaluation of local hydrology. The validation of climate patterns provides somewhat poor results; thus, the interaction among climate and hydrology needs to be explored carefully to warrant the credibility of hydrological scenarios. Overall, the spatial and temporal consistency of GCM projections, as explored here climatically and hydrologically, provides a clue about their dependability for basin scale management. [ABSTRACT FROM AUTHOR]