Hydropower dams have been rapidly developed in the upstream Mekong River Basin without considering the downstream related issues. This research aims at investigating possible impacts of six hydropower dams of the Lancang cascade in the main Mekong River on flow regimes, including the magnitude, timing, and inter-and-intra variations, of the Vietnamese Mekong Delta (VMD) based on time series of historical flow data at TanChau station as a protocol. The results show that the impacts of the first four dams in the Lancang cascade on flow regimes in the VMD are not obvious. However, flow regimes in the VMD have been significantly altered when all six dams in the Lancang cascade were completed. In flood season, median discharge and maximum water level decrease by 13.5% and 20.2% respectively. High and low stage durations decrease by 55% and 66% when six dams existed. Flows from November to February are significantly reduced, causing difficulty for irrigation in the VMD. In dry seasons, discharges generally increase while water levels decrease due to river bed incision and reduction in sediment supply from the upstream, causing an increase in tidal influence accompanied by saltwater.