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• RSPARROW was optimized by combing climatic factors and various emission sources. • Spatio-temporal trends of TN and TP loads were analyzed in the YRB on a long-time scale. • Precipitation and point source are key drivers of trends in inter-annual TN load. • Point source is the driving forces in inter-annual variation of TP load in the whole basin. The Yellow River Basin (YRB) plays a very important role in China's economic and social development and ecological security. In particular, the ecosystem of the YRB is sensitive to climate change. However, the change of nutrient fluxes in this region during the past years and its main driving forces remain unclear. In this study, a hydrologic model R System for Spatially Referenced Regressions on Watershed Attributes (RSPARROW) was employed to simulate the spatio-temporal variations in the fluxes of total nitrogen (TN) and total phosphorus (TP) during the period of 2006-2017. The results suggested that the TN and TP loads increased by 138% and 38% during 2006-2014, respectively, and decreased by 66% and 71% from 2015 to 2017, respectively. During the period of 2006-2017, the annual mean fluxes of TN and TP in the YRB were in the range of 3.9 to 591.6 kg/km2/year and 1.7 to 12.0 kg/km2/year, respectively. TN flux was low in the upstream area of the Yellow River, and presented a high level in the middle and lower reaches. However, the flux of TP in Gansu and Ningxia section was slightly higher than that in the lower reaches of the Yellow River. Precipitation and point source are the key drivers for the inter-annual changes of TN loads in most regions of the YRB. While the inter-annual variations of TP loads in the whole basin are mainly driven by the point source. This study demonstrates the important impacts of climate change on nutrient loads in the YRB. Moreover, management measures should be taken to reduce pollution sources and thus provide solid basis for control of nitrogen and phosphorus in the YRB. [Display omitted]. [ABSTRACT FROM AUTHOR]