OBJECTIVE：To provide reference for improving the mechanism of drug supervision in Guangdong-Hong Kong-Macao Greater Bay Area. METHODS ：Based on the evolutionary game theory ，the stakeholders of Guangdong-Hong Kong-Macao Greater Bay Area in the stage of drug safety supervision were identified ；the evolutionary game model was established so as to obtain the behavioral selection and evolutionary stability strategy of the each party through and put forward the suggestions for improving the mechanism of drug supervision in Guangdong-Hong Kong-Macao Greater Bay Area. RESULTS & CONCLUSIONS：Based on evolutionary game theory ，the three-party evolutionary game model of drug administration ，drug inspection and manufacturing enterprises was established. According to the model established in this study ，it could be concluded that：when the compliance cost of the production enterprise was less than the sum of the violation cost and the bribery cost minus the additional income ，or less than the sum of violation cost and punishment and reputation lossminus the additional income ，the manufacturing enterprises could achieve the equilibrium state of compliance production ；the supervision probability was inversely proportional to the supervision cost ，and strict inspection was inversely proportional to inspection cost ；compliance productivity rate and strict detection rate were in direct proportion to the intensity of supervision and penalties ；the higher the supervision probability was，the higher the strict detection rate was ，and the compliance productivity would gradually increase. It is proposed to link enterprise information files ，lay the foundation of four party cogovernance ；introduce the “cost-benefit”supervision system ，make reasonable use of the third-party inspection institutions ；clarify the boundary of personnel responsibility ，and use the intelligent system for real-time supervision so as to promote the improvement of drug safety supervision in Guangdong-Hong Kong-Macao Greater Ba y Area.