A dramatic reduction in the observed river runoff has resulted in a record-high level of dried-up days in the Huolin River catchment (HRC). In this study, we used the hydrological simulation approach of the Soil and Water Assessment Tool (SWAT) model to evaluate the influences of climate change and human activities on runoff in the HRC. The SWAT model effectively simulated the streamflow changes in the HRC with high accuracy. The R2 values were 0.71 and 0.69 for the calibration and validation periods, respectively. In addition, the Nash–Sutcliffe efficiency (NSE) index reached 0.69 and 0.66 for the calibration and validation periods, respectively. The simulation results demonstrated that the variations in runoff have mostly been caused by the combined influence of climate change and land use/land cover (LULC) changes, but the contributions of these factors varied in each period. The climate factors contributed 84.5% of runoff fluctuations before 2000 and the effect of LULC changes gradually grew after 2000. The increase in the influence of LULC changes was mainly apparent in the considerable growth of the areas of the arable land and construction land, which increased by 607 and 113 km2, respectively.