A novel method for the synthesis of antioxidant 168 has been developed in continuous flow, which has the advantages of short reaction residence time, simple operation and high safety performance. Antioxidant 168 was synthesized by esterification of 2,4-ditert-butylphenol and phosphorus trichloride in continuous flow, and the effects of reaction solvent, type and dosage of acid-binding agent, reaction temperature and reaction residence time on the yield of antioxidant 168 were investigated. The desired product was characterized by melting point, GC, 1H NMR, 13C NMR and HRMS. The results showed the optimum conditions were determined as follows: the molar ratio of 2,4-ditert-butylphenol, phosphorus trichloride and triethylamine was 3.0:1.0:3.3, the reaction temperature was 75℃, the reaction residence time was 240s. The yield of antioxidant 168 was 90%under the optimum conditions, and the purity exceeded 99%.