Abstract: To investigate the synthesis method of 16α-¹⁸Ffluoro-17β-fluoroestradiol on domestic synthesizing module, the automated synthesis was carried out through the reaction of 3-O-(methoxymethyl) -16,17-O-sulfuryl-16-epiestriol (MMSE, 1 mg) as precursor with ¹⁸F^- at 105 ℃ for 15 min in sealed system on domestic synthesizer, then 0.8 mL 1 mol/L HCl dissolved in 7.2 mL acetonetrile was added in three parts to the reaction vessel for hydrolysis and hydrolysis reaction was performed at 105 ℃ for 6 min. The final reaction solution was purified by HPLC to give ¹⁸F-FES. Preparation of ¹⁸F-FES on domestic synthesis module was in the uncorrected synthesis yield of 8.2% (corrected synthesis yield 12.8%). Total synthesis time was about 70 min and radiochemical purity was higher than 98%. The product had good stability at room temperatur. ¹⁸F-FES injection can be prepared on domestic synthesis module and the quality can meet the requirements of radiopharmaceuticals for clinical use.