One of the main characteristics of water-bearing system in karst area is that the pipelines of sinkholes of the developing soluble rock are connected with the underground water network. The precipitation and its surface runoff can be quickly poured into the underground river system through the pipelines, the underground complex hydrology changed the aquifer's transmission mode and the transmission speed and quantity of the non-point source pollutants in the vertical and horizontal directions selected. The karst area in the Poyang Lake Watershed is selected as the object of non-point source pollution. This study examined the characteristics of karst water system, the hydrological process of introduce holes, underground river, and the main nutrient transfer process. The original hydrological cycle of SWAT, the related algorithms, the single feature of the non-point source pollution simulation in the loose homogeneous medium basin was modified. This study established the non-point source pollution model suitable for karst watershed and the corresponding simulation method. This modified model, through a controlled simulation method and a sensitivity analysis, is used to quantitatively evaluate the impact of the karst characteristics of water, including sinkholes, underground stream and river on nitrogen and phosphorus and other major non-point source of pollutant transport and its correspondent time and space effect. Furthermore, the interaction and conversion mechanism of sinkholes, underground stream, river with the surface-underground hydrology and nutrient salt was analyzed. The results showed that the karst characteristics had an increasing effect on the nitrogen and phosphorus load in the watershed. The increase of total phosphorus was significantly greater than the increase of total nitrogen, and the increase of total phosphorus and total nitrogen was 0.86% and 2.12%, respectively. The increase of vegetation karst index can cause the increase of the output of soluble phosphorus and organic phosphorus in the watershed, followed by the output of organic nitrogen and nitrate and nitrogen. The sinkholes changed the way of rainfall and increased the production of organic phosphorus and organic nitrogen, with the incremental change in the range of 0-0.7 kg/ha and 0-0.3 kg/ha, respectively.