The invention discloses a synthesis method of a diesel fuel depressant. The synthesis method comprises the following steps of: carrying out one-pot polymerization reaction in an initiating agent and a solvent by taking poly-alpha-methylacrylic acid high-carbon alcohol ester, a polar nitrogen compound, vinyl acetic ester and vinyl benzene as raw materials; and mixing a reactant with twain and span to obtain a target product, i.e., the diesel fuel depressant. The synthesis method is free of aftertreatment and simple in process; the synergic initiating agent is adopted to initiate the polymerization reaction, and the raw materials are dropwise added in twice and sufficiently react; the reaction conditions are mild, and the polymerization reaction is carried out in the mixed solvent, so that the reaction temperature range is widened, and the reaction is more easily carried out; and a special raw material proportion is adopted, so that the produced diesel fuel depressant has good perceptibility for diesel fuel with high paraffin content and favorable cold filter plugging point reducing performance, and the low-temperature performance of the diesel fuel is remarkably improved.