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Scientific understanding of the scale effects of landscape structure on water quality is essential for national land planning and water environment management. However, there is no consensus on the optimal spatial landscape scale affecting water quality. To this end, we developed a novel mix scale division method, which is consist of the intersection of sub-basin, stream buffer zone and circular buffer zone. Based on the water quality data from 113 monitoring stations of the Yellow River Basin, we quantitatively identified the spatial scale effects of various landscape indexes on water quality, as well as the nonlinear response of the water quality along the gradient of landscape indicators in the Yellow River, by using the Redundancy analysis (RDA) and Generalized Additive Model (GAM). We show that landscape indexes related to buildup and agricultural lands had significant impact on water quality changes, and this impact was more influential during the rainy season compared with the dry season. We also identified that the optimal scale and landscape pattern corresponding to the main non-point source factors, i.e., COD Cr , total nitrogen (TN), and total phosphorus (TP). The variations of these three water quality indicators were predominated by buildup land (B-CA) at sub-basin (with a contribution percentage of 43.7%), agricultural land (A-CA) at the scale of stream buffer (bs) = 1000 m and circular buffer (bc) = 20 km (50.2%), and the largest patch index of agriculture (A-LPI) at the scale of bs = 1000m and bc = 25 km (41.7%), respectively. The B-CA>50000 ha at the sub-basin scale and A-LP = 50% at the mixed scale (bs = 1000m, bc = 25 km) would accelerate the deterioration of water quality. Results implied that water quality could be improved by implementing landscape regulation within an appropriate scale and considering the non-linear effects of landscape structure on water quality. • Developing a novel mixed buffer zone division method to analyze the influence range of landscape structure on water quality. • Locating the optimal scales of different landscape indices on water quality. • The nonlinear effect of the landscape on the water quality is found. • Water quality degradation in YRB is susceptible to human activities, particularly the agricultural landscape. [ABSTRACT FROM AUTHOR]