This paper reported an optimum preparation process of 3-Picoline by mild liquid phase reaction of acrolein based on single factor design method. The reaction was carried out in the solvent of ethylene glycol monobutyl ether at temperature 140℃ for one hour, the mole ratio of acrolein and acetic ammonium and ethylene glycol monobutyl ether was 1:8:33, the mass ratio of acrolein and catalyst SO24-/TiO2-HZSM-5 was 1:1.4, and the mass percent of acrolein in n-butyric acid was 8%. Under the optimization conditions, the conversion rate of acrolein could reach to 100% and the selectivity of 3-picoline with a yield 49.92%