The objective of this study was to simulate the hydrologic characteristic and water quality of 3S rivers system (Sekong, Sesan and Srepok) using SWAT model (Soil and Water Analysis Tool). Agriculture and forest are the main land use types in this basin accounting for more than 80 % of the total area. Therfore, nitrogen and phosphorus were selected to be parameters for water quality assessment. SWAT-CUP model was applied to calibrate the model for stream flow and water quality based on SUFI-2 (Sequential Uncertainty Fitting version 2) method. The model performance has been assessed by three statistical indices, including coefficient corellation (R2), Nash-Sutcliffe efficient coefficience (NSE) and percentage Bias (PBIAS). The results showed that SWAT model was well calibrated for simulating the streamflow and water quality with the values of R2 greater than 0.5 except for the Attapeu and Kontum stations, and of PBIAS less than 10 % and 35 % for streamflow and water quality, respectively. The well-calibrated SWAT model can be applied in predicting the hydrology and water quality for other application. Furthermore, it is a tool supporting the policy makers to offer a suitable decisions regarding the sustainable river basin management.