With the global spread of the COVID-19 epidemic, the impact of a series of chain reactions triggered by public health security issues on the economic prosperity has become the primary concern of today’s society. It makes us more deeply aware of the importance of developing health care. Therefore, it is very important to re-pay attention to the impact of long-term potential public health security problems on the degree of economic prosperity, and then to find the external factors that affect public health security problems and the transmission path of their effects on the degree of economic prosperity.For the above purpose, this paper constructs a dynamic spatial Durbin model and uses the panel data of 31 provinces in China from 2007 to 2017 to study the spatial linkage mechanism of medical system, public health security and economic prosperity. The study finds that: Although the current treatment capacity is weak, under the existing medical system, the level of medical security and treatment capacity can adjust the negative impact of medical security problems on economic growth, the activity of financial institutions and the activity of the stock market, and there is an obvious spatial spillover effect. On this basis, the mechanism of public health security on economic prosperity is further analyzed. It is considered that public health security problems inhibit economic growth, financial institution activity, stock market activity, and spatial spillover effects to varying degrees by hindering exports, FDI and the upgrading of industrial structure. It is worth noting that the spatial spillover effect of exports on economic growth is not significant, and the spatial spillover effect of FDI on economic growth and financial institution activity is not significant. Finally, the regression results of night lighting data once again confirm the existence of the regulation effect of medical system and the transmission mechanism of public health security problems. Among the three transmission paths, FDI accounts for the largest proportion, followed by exports, and the proportion of advanced industrial structure is relatively small.The marginal contribution of this paper may be reflected in the following three aspects: First, the economic growth, financial institution activity and stock market activity are brought into the index system of economic prosperity at the same time, and the research perspective is extended to the spatial dimension. From the perspective of spatial spillover effect, this paper analyzes the spatial geographical relationship between public health security and economic prosperity. The important role of spillover effect in promoting regional coordinated development is analyzed. Second, it analyzes the mechanism of the medical system in reducing the impact of public health security problems on economic prosperity, in order to strengthen public health investment and personnel training, improve disease prevention and control conditions, optimize the national disease prevention, and control system to provide reference. Third, it further analyzes the transmission mechanism of public health security issues affecting economic prosperity through exports, FDI and advanced industrial structure, to provide support for adjusting the trade structure, further improving the policy of attracting investment, and promoting the transformation and upgrading of the industrial structure. In addition, the authenticity of the index system of economic prosperity is verified by using the night light luminance value (DN), which avoids the data distortion and minimizes the error of statistical regression.