Zhuzhaoxin River is an important river in Nansi Lake Basin, and it is of great significance to study the runoff of the river basin and the west plain area of Nansi Lake. This paper chooses a distributed hydrological model-SWAT and uses parameter sensitivity analysis, parameter rate determination and uncertainty analysis based on Sufi-2 algorithm of SWAT-CUP program, to simulate Zhuzhaoxin River Basin monthly runoff process in 2008-2014. The results showed that: The correlation coefficient R2 and NS efficiency coefficient of the monthly runoff and the validation period were all greater than 0.85, indicated that the SWAT model was applicable in Zhuzhaoxin River Basin. The sensitivity analysis results showed that several hydrological parameters have different degree of correlation with runoff, with 13 the most sensitive, such as compensation coefficient of vegetation transpiration, the base flow of α factor of the bank regulation, and shallow groundwater runoff coefficient. The introduction of the CMADS meteorological data set as the driving data set of the hydrological model in the basin has achieved the desired effect in the area with relatively low meteorological station density.