The invention discloses a preparation method of large-molecular weight perfluoropolyether acyl fluoride by negative-ion ring opening polymerization of hexafluoropropylene oxide. The negative-ion ring opening polymerization is carried out on hexafluoropropylene oxide to obtain the acyl fluoride of which the structural formula is CF3CF2 (CF2OCF (CF3)) nCOF under the condition of the composite catalyst which consists of a fluoride-containing organic solvent, alkali metal fluoride and polybasic ether, wherein the average molecular weight of the acyl fluoride is greater than 2000, molecular weight distribution is narrow, and the structure of the acyl fluoride can be converted into the structure of which the tail end is -OH, -COOH and -NH2 due to the activity of the acyl fluoride, so that the technology can be further used for the synthesis of polyester resin, epoxy resin and the like.