It is essential to evaluate the ecological risk for the estuary cities area for the environmental restoration of the estuary. The ecological risk of six city areas from the Pearl River Estuary were evaluated by using the relative risk model. The relative risk assessment method was developed by considering the river network density in the sub-region. The results indicated that Dongguan had the largest ecological risk pressure with total risk scores as high as 10,846.3, and Hong Kong had the lowest ecological risk pressure with total risk scores up to 4,104.6. The greatest source was domestic sewage with total risk scores as high as 1,798.6, followed by urbanization and industry. Oxygen-consuming organic pollutants, organic toxic pollutants and nutrients were the major stressors of the water environment. In terms of habitats, the water environment was enduring the greatest pressure. For the endpoints, water deterioration faced the largest risk pressure.