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Panax notoginseng cultivation planting conditions are harsh and require high soil moisture and slope of cultivated land, plus it takes 3–7 years from planting to harvesting. At present, the continuous crop barrier of Panax notoginseng has not been solved, which makes the arable land suitable for planting significantly reduced. And yet, there is almost no report on the impact of coupling water and slope on the growth of Panax notoginseng. Therefore, this study aims to explore the effects of different irrigation levels and slopes on soil water content (SWC) in the root zone, soil nutrient content, root characteristics, yield, water use efficiency (WUE), partial fertilizer productivity (PFP) and economic benefits of Panax notoginseng. During 2018–2020, a field experiment was conducted in the Panax notoginseng growing seasons with three irrigation levels (I 1 : 70–75% θ FC , I 2 : 75–80% θ FC , I 3 : 80–85% θ FC) and three slopes (S 1 : 2.43°, S 2 : 6.38°, S 3 : 16.38°). The results evidenced that soil water and nutrient content increased with increasing irrigation and decreased with increasing slope. The yield of Panax notoginseng , root morphological characteristics, WUE, PFP, and economic benefits showed a trend of increasing first and then decreasing with the increase of irrigation amount and slope, which increased with the increase of planting years. These parameters reached their maximum at the irrigation I 2 (75–80% θ FC) and slope S 2 (6.38°) treatments. Thus, based on the results of this study, medium irrigation I 2 (75–80% θ FC) and slope S 2 (6.38°) should be considered as the best slope and water management strategy to obtain both high Panax notoginseng yield and economic benefits. Through establishing a multi-objective optimization model with binary quadratic regression analysis. It was indicated that Panax notoginseng yield, WUE, PFP, and economic benefits simultaneously reached ≥ 98% of their maximum values when irrigation interval was 152–193 mm and slope interval was 5.4–9°. In summary, the results obtained in this study have important practical significance for the water management of Panax notoginseng cultivation in slope farmland in Yunnan Province, China. [Display omitted] • Water regulation technology for Panax notoginseng cultivation on sloping land was proposed. • Soil nutrient content and Soil water content gradually decreases with increasing slope. • I 2 S 2 treatment obtain maximum yield and economic efficiency. • Irrigation interval of 152-193 mm and slope interval of 5.4-9° determined to make yield, economic benefits, PFP and WUE reach ≥ 98% maximum. [ABSTRACT FROM AUTHOR]