After the 12.5 m deep water channel of Yangtze estuary extends to Taicang, for making full use of Yangtze estuary deep channel regulation works, making better use of lower Yangtze River harbors and channels, and promoting the social and economic development of the Yangtze delta zone, it is in an urgent need to extend the deep water channel to Nanjing. The south Liu river reach is complex in natural condition, with combined influence by river discharge and tide, so it is necessary to assure the design lowest navigation water level in order to suitably and economically carry out the main channel regulations and exploitation of the middle and lower Yangtze River according to the present condition. For the river reaches without tide influence or with insignificant tide influence, the design lowest navigation water level should adopt the synthetic duration curve method, while for those with obvious tide influence, cumulative frequency as 90% of low tide levels should be adopted. The south Liu river reach is influenced by both tide and river discharge, thus further research is necessary to study the scope of applications of two methods.