National laboratory is an important platform for national scientific and technological innovation, and its importance in national scientific and technological innovation system has been constantly enhanced. At present, the overall development of national laboratories is still in the exploratory stage in China. It is urgent to grasp management and operational experience to promote the construction of first-rate national laboratory. The United States has established a complete national laboratory system. Taking the Frederick National Laboratory for Cancer Research under U.S. Department of Health and Human Services as an example, we analyzed its development context, operation mechanism, core research capabilities and achievements, fund revenue and expenditure, sharing mechanism of user facilities, education and social services, and open-innovation. By excavating the operational experience, it will provide reference and inspiration for the construction of biomedical national laboratories in China.