Huaihe River basin is located in central-eastern China, and it stands between the south-north climatic transitional zone. Varied kinds of weather systems mutually interlock and mutually effect, which forms a typical ecologically fragile area, and Huaihe River is also a sensitive area of climate change. In order to fully understand the impact of climate change to runoff in the upper-middle reach of Huaihe River basin, the paper applied the data of monthly runoff from 1971 to 1990 for the calibration and the data from 1991 to 2014 for verification by using automatic adjusting and parameters adjusting of SWAT model. The evaluation results showed that the Nash-Sutcliffe efficiency coefficient and linear determination coefficient were more than 0.8, and the relative error of simulation (Re) was less than 1%, indicating that the model could effectively reproduce the rainfall-runoff process of monthly scale. The annual runoff depth didn't show obvious linear trend in general, while the upstream and the southern part of the runoff depth of the sub-basin were linear decreasing, and other areas were increasing. The annual evaporation and water percolation past bottom of soil profile in watershed for the year contributed more to the change of annual water balance elements. The average temperature, precipitation and evaporation were the critical factors of the changes of hydrological elements in the upper-middle reach of Huaihe River basin using principal component analysis. Eliminating the influence of human factors, the annual water resources were slightly decreased in the upper-middle reach of Huaihe River basin in 1971-2014, which might be the result of significantly increase of the annual average temperature, slightly decrease of annual precipitation, and notably decrease of annual evaporation. This study could provide a scientific basis for the management of water resources and policy-making in the upper-middle reach of Huaihe River basin.