The invention discloses a genetic engineering strain of high-yield secondary metaboliteFumagillin as well as a construction method and application of the genetic engineering strain, and the genetic engineering strain is obtained by taking aspergillus fumigatus as a chassis bacterium through hosA gene knockout or hosA catalytic active sitemutation. According to the method, a hosA gene knockout strain (delta hosA) and catalytic active sitemutation strains (HosAD133A, HosAH175A and HosAD210A) are constructed by means of molecular biology, and the mutant strains are subjected to liquid or solidfermentation under the culture condition of 37 DEG C, so that the yield of Fumagillin can be remarkably increased. According to the method disclosed by the invention, the inhibition on a Fumagillin biosynthetic pathway is relieved and the metabolic flux is enhanced by utilizing the activity change of histone deacetylase caused by hosA defects, and an efficient and directional production method for high-yield Fumagillin is provided, so that the method has an important industrial application value.