The Dinh An Estuary is one of the Nine Dragon estuaries of the Mekong River. An intational navigation channel was built in the estuary for vessels traveling from the South China Sea to the southwest area of Vietnam and then to Phnom Penh, Cambodia. The morphological evolution of the navigation channel is complicated and unstable. The back siltation intensity in the navigation channel has largely increased and been concentrated in the curvature segments of the channel since 1980. In this study, based on simulation results and measured data, five key factors that influence the back siltation in the navigation channel were systematically analyzed. These factors included the increasing elevation gap between the channel and the nearby seabed, the disadvantageous hydrodynamic conditions, sediment transport, mixing of saltwater and freshwater, and wave effects in the navigation channel. It is shown that the back siltation to a large extent results from the low current velocity of the secondary ocean circulation, which often occurs in the curvature segments of the channel. Suspended sediment also settles in the channel due to the decrease of the current velocity and the sediment transport capacity when flow passes through the channel. The changes of hydrodynamic conditions are responsible for the majority of the severe siltation in the curvature segments of the navigation channel.