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Meteorological and hydrological droughts can bring different socioeconomic impacts. In this study, we investigated meteorological and hydrological drought characteristics and propagation using the standardized precipitation index (SPI) and standardized streamflow index (SSI), over the upstream and midstream of the Heihe River basin (UHRB and MHRB, respectively). The correlation analysis and cross-wavelet transform were adopted to explore the relationship between meteorological and hydrological droughts in the basin. Three modeling experiments were performed to quantitatively understand how climate change and human activities influence hydrological drought and propagation. Results showed that meteorological drought characteristics presented little difference between UHRB and MHRB, while hydrological drought events are more frequent in the MHRB. In the UHRB, there were positive relationships between meteorological and hydrological droughts, whereas drought events became less frequent but longer when meteorological drought propagated into hydrological drought. Human activities have obviously changed the positive correlation to negative in the MHRB, especially during warm and irrigation seasons. The propagation time varied with seasonal climate characteristics and human activities, showing shorter values due to higher evapotranspiration, reservoir filling, and irrigation. Quantitative evaluation showed that climate change was inclined to increase streamflow and propagation time, contributing from -57% to 63%. However, more hydrological droughts and shorter propagation time were detected in the MHRB because human activities play a dominant role in water consumption with contribution rate greater than (-)89%. This study provides a basis for understanding the mechanism of hydrological drought and for the development of improved hydrological drought warning and forecasting system in the HRB.