The invention discloses a preparation method of 4-bromo-2, 3, 5, 6-tetrafluorobenzeneacetic acid, the structure of which is shown in formula one. The method comprises the following steps: (a) under the protection of nitrogen and a temperature ranging from 40 to 120 DEG C, 2, 3, 4, 5, 6- bromopentafluorobenzene with the structure shown in formula two and diethyl ester with the structure shown in formula three perform nucleophilic substitution with the catalysis of cuprous salt and under the effect of strong base, and an intermediate 2-(4-bromo-2, 3, 5, 6-phenyl tetrafluoride) diethyl ester with the structure shown in formula four is obtained; inorganic base and water are added to2-(4-bromo-2, 3, 5, 6-phenyl tetrafluoride) diethyl ester to perform hydrolysis under reflux condition; after complete hydrolysis, heating and decarboxylation, 4-bromo-2, 3, 5, 6-tetrafluorobenzeneacetic acid is obtained. The preparation method has the advantages that, the low toxic substance diethyl ester is used as the nucleophile, and the ethanol, a small amount of CO2 and other substances produced during the hydrolysis decarboxylation have less environment pollution, so the method has environmental advantages.