The invention discloses a pentafluorophenol isonitrile polymer and a preparing method and application thereof. The structure of the pentafluorophenol isonitrile polymer is shown as the following general formula (see the formula in the description), wherein the polymerization degree n=50-200. The preparing method includes the steps that pentafluorophenol isonitrile monomers are polymerized under palladium catalysis into the pentafluorophenol isonitrile polymer, and the pentafluorophenol isonitrile monomers are polymerized under nickel catalysis into the pentafluorophenol isonitrile polymer. The pentafluorophenol isonitrile polymer is used for ester exchange with compounds containing amino groups and hydroxyl groups and is high in exchange efficiency, operation is easy, synthesis is simple, and the synthesis steps are simplified.