Watershed Best management Practices (BMPs) spatial optimal layout would be affected by uncertainty, and there are still three problems which are worthy of studying in the present studies of watershed BMPs spatial optimal layout under uncertainty: (1) how to integrate multiple uncertainties in optimization model effectively; (2) how to avoid subjective weight in multi-objective uncertainty model; (3) how to develop more elastic schemes for uncertainty impact. To solve the mentioned problems, this study takes Zhegao river watershed, China as an example, interval stochastic fuzzy fractional programming (ISFFP) integrated with SWAT hydrology model is applied for BMPs spatial optimal layout in watershed to reduce non-point source (NPS) pollution. The result shows that the ISFFP method could solve the problems effectively, and the method could be adapted to different types of uncertainty, also the method has seldom been used in uncertainty BMPs spatial optimal layout, and the method is worth of popularization.