Mid- to long-term runoff forecasting is important to China. Forecasting based on physical causes has become the trend of this field, and recognition of key factors is central to recent development. Here, global sensitivity analysis based on back-propagation arithmetic was used to calculate the sensitivity of up to 24 factors that affect runoff in the Nenjiang River Basin. The following five indices were found to be key factors for mid- to long-term runoff forecasting during flood season: Tibetan Plateau B, index of the strength of the East Asian trough, index of the area of the northern hemisphere polar vortex, zonal circulation index over the Eurasian continent and index of the strength of the subtropical high over the western Pacific. The hydrological climate of the study area and the rainfall–runoff laws were then analysed in conjunction with its geographical position and topographic condition. The rationality of the results can be demonstrated from the positive analysis point of view. The results of this study provide a general method for selection of mid- to long-term runoff forecasting factors based on physical causes. Copyright © 2012 John Wiley & Sons, Ltd.