Under the background of Healthy China, China is gradually promoting the improvement of drug guarantee mechanism for rare diseases, which is not only the inherent demand of high-quality medical insurance development in China, but also a key task of further deepening the reform of medical system. This paper analyzes the three pairs of unbalanced relationship between the reality of rare disease expense guarantee and the people's demand for medical treatment and insurance by analyzing the current policy of rare disease expense guarantee and the situation of local reform. Finally, based on the national conditions, this paper puts forward the direction of improving the comprehensive guarantee mechanism of rare disease expenses, which is to “do two basic work well” and “play three roles”.