Abstract: With the development of modern science and technology, more and more scientific research need to keep combined with practical application. Therefore, there are more and more cleaning rooms built for micro-nano fabrication in universities. Furthermore, it is necessary to formulate the operational regulations and management. In this article, it is discussed that how to make it operate normally and safely by the three aspects of environmental control, operational specification and personal management. Sequentially, it ensures the quality of samples and guarantees for scientific research in colleges and universities.