Rapid development and urbanization in recent years have contributed to a reduction in freshwater discharge and intensified saltwater intrusion in the Pearl River Delta. This comprises a significant threat to potable water supplies and overall estuary ecosystem health. In this study, the environmental flows of the Modaomen Estuary, one of the estuaries of the Pearl River Delta in China, were determined based on the salinity demand of keystone species and the linear relationship between river discharge and estuarine salinity. The estimated minimum and optimal annual environmental flows in the Modaomen Estuary were 116.8 × 10⁹ m³ and 273.8 × 10⁹ m³, respectively, representing 59.3% and 139.0% of the natural runoff. Water quality assessments in recent years indicate that the environmental flows have not been satisfied most of the time, particularly the optimal environmental flow, despite implementation of various water regulations since 2005. Therefore, water regulations and wetland network recoveries based on rational environmental flows should be implemented to alleviate saltwater intrusion and for the creation of an ideal estuarine habitat.