The river function regionalization is the foundation to regulate and guide the river development and protection. In the context of the river function classification, this paper elaborates on the connotation and the principle of the river function regionalization, constructs a river function regionalization system that includes four regions (protect zone, retention zone, development and utilization zone, and buffer zone) and eleven sub-regions, and gives division indexes and methods. The river function regionalization is used in the main stream of the Yellow River as an example. The Yellow River is divided into 21 primary functions including three protect zones, five buffer zones, eleven development and utilization zones. The results show that the proposed river function regionalization system and methods are rational and feasible, and can regulate and guide the river development and protection as a new management tool.