In order to study the response of impervious surface expansion on runoff, this paper establishes the HSPF model in the upper and middle reach of the Weishui River Basin, and constructs impervious surface expansion scenario from 2000 to 2015. The results showed that the HSPF model has high precision on monthly runoff simulation, and is feasible in the studing area. The impervious surface expansion of the studying area will cause a small increase in annual runoff. The impact of impervious surface expansion on runoff during dry season is greater than that on runoff during flood season, and the impervious surface expansion has the greatest impact on the annual runoff depth of dry years, followed by the flat water years and the smallest in wet years. The runoff response of the impervious surface expansion in the main urban area is consistent with the trend of the whole study area, but its response is more severe than that of the whole study area.