To improve the medical insurance and assistance system for major diseases is an important measure to strengthen and improve the people's livelihood with the development of China. At present, the system also faces five major challenges, such as the difficulty in accurately anchoring the target of assistance, the difficulty in ensuring that the residents should be fully insured, the difficulty in ensuring the treatment of medical expenses, the difficulty in inter-regional system coordination, and the difficulty in developing supplementary support such as charity mutual assistance and commercial health insurance. Therefore, this paper suggests that we should transit from the preferential policy of concentrated tackling to the general policy of normalized assistance, expand from guarantee of income poverty to expenditure poverty, and shift from extensive management to fine management.