Under the strategic background of Healthy China, analyzing the efficiency and influencing factors of government healthcare expenditure in the Yangtze River Delta region can provide reference opinions for promoting the high-quality development of its healthcare industry. Based on the panel data of 41 cities in the Yangtze River Delta region from 2016 to 2021, DEA-BCC model and Malmquist index are used to analyze the efficiency of health expenditure in the Yangtze River Delta region from the static and dynamic dimensions, and the restricted dependent variable Tobit model is used to analyze its influencing factors. The expenditure efficiency in the Yangtze River Delta region is relatively high, but there are significant differences across regions. The low scale efficiency and declining technological progress in most regions have become key constraints on expenditure efficiency. The per capita GDP, urbanization rate, and expenditure efficiency are significantly positively correlated, while population density, proportion of medical and health expenditure, fiscal decentralization, and expenditure efficiency are significantly negatively correlated. The number of ordinary higher education students per 10000 population has a certain impact on expenditure efficiency, but it is not significant. On this basis, suggestions are proposed to optimize the efficiency of healthcare expenditure in the Yangtze River Delta region.