MAH system is a drug listing system, which is internationally recognized, features the diversification of production form, freedom of technology transfer, saving market resources, improving the quality of government administrative supervision and so on. In 2016, China carries out the drug marketing authorization holder system(MAH) in 10 provinces(cities), such as Beijing and Shanghai. Based on the path-dependence problem of China’s drug listing system, an evolutionary game model is constructed, analyzing the internal institutional changes made up by drug research and development agencies, and pharmaceutical production enterprises, and external institutional changes made by governments and consumers, and the evolution path of game subject behavior is deeply studied. Research has shown that the internal system and the external system path dependence are the main reasons that restrict the development of China’s pharmaceutical industry and the insufficient power of the new drug research and development. The internal institutional changes of drug listed companies mainly affect drug research and development institutions and drug production enterprises through scale effect and adaptability expectation, thus leading to the path dependence of the internal system of drug listing; The external institutional change of drug market is mainly influenced by the learning effect and the coordination effect of the government and consumers, thus generating the path dependence of the external system of drug listing. Based on this, Matlab is used to carry out numerical analysis to discuss the optimal stability strategy in the process of drug system change. And it has explained the path dependence of the village during the transformation of MAH system in China, which provides some reference for perfecting the path dependence of MAH system in our country.