The invention discloses acetal bond-containing polyethylene glycol, a derivative and synthetic methods of the acetal bond-containing polyethylene glycol and the derivative. The synthetic method of the acetal bond-containing polyethylene glycol comprises the following steps: under the water-free inert gas condition, by taking 2-(vinyloxy)ethanol and acetyl chloride as substrates, synthesizing 2-ethyleneoxy ethyl acetate; then carrying out reaction on the 2-ethyleneoxy ethyl acetate and allyl alcohol under the ice water bath condition, and adding p-toluene sulfonic acid hydrate as a catalyst to synthesize 2-(1-(allyloxy) ethoxy) ethyl acetate; then carrying out hydrolysis on the 2-(1-(allyloxy) ethoxy) ethyl acetate under the alkaline condition to obtain 2-(1-(allyloxy) ethoxy) ethanol; and finally under the condition with presence of DPMK as the catalyst, adding ethylene oxide for polymerization to obtain the acetal bond-containing polyethylene glycol. The invention provides the synthetic methods of the acetal bond-containing polyethylene glycol and the derivative thereof. Double bonds at a terminal of the synthesized polyethylene glycol can be substituted with a functional group such as a hydroxyl group and the like, the hydroxyl group can also be substituted with other functional groups, and thus a series of polyethylene glycol with different functional groups at the terminal are obtained. In addition, used raw materials are relatively common, a synthetic route is simple, the pollution performance is low, reaction has higher efficiency, and popularization and application are facilitated.