The direct settlement between medical insurance fund and pharmaceutical enterprises is beneficial to promoting the in-depth development of centralized volume-based drug procurement, and provides a new method to control the unreasonable rise of medical expenses as well. However, the adjustment of the routine settlement process also brings new risks to the safe operation of the fund. On the basis of a comprehensive analysis of the change of settlement methods, this paper uses the risk management theory to identify the risks of centralized volume-based drug procurement and direct settlement, analyzes the causes of risk, and puts forward the countermeasures. It is suggested improving the procedural and standardized construction level of medical insurance business, and promoting the implementation of the direct settlement policy in a steady and orderly manner.