This study implemented the rainfall-runoff analysis of the Mekong River basin using the SWAT (Soil and Water Assessment Tool). The runoff analysis was simulated for 2000~2007, and 11 parameters were calibrated using the SUFI-2 (Sequential Uncertainty Fitting-version 2) algorithm of SWAT-CUP (Calibration and Uncertainty Program). As a result of analyzing optimal parameters and sensitivity analysis for 6 cases, the parameter ALPHA_BF was found to be the most sensitive. The reproducibility of the rainfall-runoff results decreased with increasing number of stations used for parameter calibration. The rainfall-runoff simulation results of Case 6 showed that the RMSE of Nong Khai and Kratie stations were 0.97 and 0.9, respectively, and the runoff patterns were relatively accurately simulated. The runoff patterns of Mukdahan and Khong Chaim stations were underestimated during the flood season from 2004 to 2005 but it was acceptable in terms of the overall runoff pattern. These results suggest that the combination of SWAT and SWAT-CUP models is applicable to very large watersheds such as the Mekong for rainfall-runoff simulation, but further studies are needed to reduce the range of modeling uncertainty.