Abstract: A two-step approach was employed to synthesize a liposoluble antioxidant dihydromyricetin linoleic acid ester (DMYL) that can improve the lipid solubility and bioavailability of dihydromyricetin (DMY). To begin, linoleic acid was reacted with phosphorus trichloride to produce linolenic acid chloride; Next, using ethyl acetate as the reaction system, DMY was esterified with linolenic chloride to produce DMYL with different degrees of esterification (DS). After being purified with ethanol and petroleum ether, the synthesized product (DMYL) was scanned infrared. The results revealed that DMY had an absorption peak at 1 634.01 cm^-1, which is the characteristic absorption peak of carbonyl groups, whereas DMYL had an absorption peak at 1 743.89 cm^-1, which is the characteristic absorption peak of ketone. The data indicated that ester linkages had formed in DMYL. In the single factor experiments, the effects of substrate mass ratio, amount of catalyst phosphoric acid added, reaction temperature and reaction time on the esterification degree were studied. The best substrate mass ratio determined by single component experiments was 1:3. The ideal addition amount of phosphoric acid was 40 μL/g. The optimal reaction temperature was 45℃. The optimal reaction time was 8 hours. On the basis of single factor experiments, response surface methodology was utilized to investigate the effects of substrate mass ratio, amount of catalyst phosphoric acid supplied, and reaction temperature on the DS. A multiple regression model equation was established, and optimized process conditions were obtained. The results showed that the substrate mass ratio (m/m) was 1:3.2, and the amount of phosphoric acid added was 36 μL/g. The reaction temperature was 44℃, and under these conditions, the degree of esterification of DMYL could reach 3.01%±0.02%. In summary, the model can predict the preparation process of dihydromyricetin linoleic acid ester well, and provide theoretical basis for the full development and utilization of dihydromyricetin.