Climate change adversely affects the hydrological cycle at the basin level. This study integrated two models, the Soil and Water Assessment Tool (SWAT) for future climate prediction, and Water Evaluation and Planning (WEAP) for the simulation of water quantity in the Hongshui River Basin (HRB), to evaluate the impacts of climate change, which plays a significant role in the lives of inhabitants downstream of the basin. Downscaled monthly rainfalls and temperatures under four Representative Concentration Pathways (RCPs) emission scenarios from five global circulation models (GCMs) were used to generate streamflow using the SWAT model. Streamflow data (1991–2001) were used to calibrate and validate, with the period of 1991–1997 used for calibration and that of 1998–2001 used for validation. Six scenarios were established to evaluate the response of the basin under socio-economic scenarios. The simulated results show that precipitation and streamflow would likely undergo a slight increase. The available water resources would be sufficient to meet the existing needs until 2050. The results indicated that no water shortages exist under socio-economic, low, and medium climate change emission scenarios, however the basin will experience a water shortage under the high climate change emission scenario (RCP-8.5). The study proposed that, to ensure the sustainability of water resources, better long-term management policies are required to be implemented in the basin and to meet future downstream water needs.