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Although El Niño-Southern Oscillation (ENSO) has been widely confirmed to have significant impacts on climate change in Asia, it is unknown whether the climate change in the Yangtze River Basin (YTR basin) is related to the operation of the Three Gorges Reservoir, which is the world's largest hydropower station. In this study, we used the Standardized Precipitation Evapotranspiration Index (SPEI) as an indicator of climate change and found that the mutation period of the YTR basin was 2003-2006 based on three mutation tests. By analyzing the trends of the SPEI and five related meteorological factors before and after 2003, it was found that the construction of the Three Gorges Reservoir increased the relative humidity and provided a more humid climate for the downstream basin. The relationships between drought events and ENSO and the water level of the reservoir indicated that the basin was more prone to drought in El Niño years and the Three Gorges Reservoir could alleviate agricultural drought in the downstream basin. The spatial impacts of the Three Gorges Reservoir on regional climate change were more pronounced, while the impact of ENSO could not be reflected at the station scale.