Abstract Through the catalytic reaction test of five kinds of catalysts, including HZSM-5, HY, 13X, ZnCl2 and C25, and a higher activity zeolite C25 was chosen as catalyst and acetic anhydride was applied as acylating agent in the Friedel-Crafts acylation reaction of thiophene at atmospheric pressure. The effects of higher reaction temperature, the raw material ratio, the additional amount of solvent acetic acid, and the different concentrations of nitric acid modified catalysts on the Friedel-Crafts acylation reaction of thiophene were investigated principally. When the reaction temperature is 80 ℃, the suitable reactive conditions are: the mole ratio of thiophene to acetic anhydride is 1∶2, reaction time 5 h, the conversion of thiophene up to 97.23%. The catalytic activity was greatly improved when the acetic acid was added; the amount of acetic acid account for 8.72% of the total materials, reaction time 5 h, the conversion of thiophene was increased by 1.3%; the catalytic activity was up to the best when the zeolite was modified by 0.5 mol/L nitric acid. Meanwhile, the research on acylation reaction of gas thiophene was conducted by fixed bed reactor, and found that the best temperature was 92 ℃. Finally, the reactive products were refined to get the purity of 2-acetyl thiophene up to 99.90%.