Reasons for the errors in runoff simulations for large-scale watersheds are discussed. BTOPMC (Block wise use of TOPMODEL with Muskingum-Cunge flow routing method) was used to simulate hydrological processes in the Mekong river basin. The Model was calibrated for the year 1987 and verifications were carried out for the years 1993 and 1994. The digital stream network was created after removing depression points in the original Digital Elevation Model (DEM). Discussion of the reasons for the differences between simulated and observed runoff values is done using daily hydrographs at five stations in the lower Mekong river basin. Not only the physical characteristics of watershed such as topography, vegetation, geology and soil but also the human activities such as paddy cultivation and reservoir operations control the hydrological processes in a watershed. BTOPMC, coupling with human activities and reservoir water operations can be used to simulate runoff in large-scale watersheds.