β-cyano ketones are important fine chemical intermediates, in which cyano groups can be converted into amides, amines, carboxylic acids and their derivatives, aldehydes, ketones, alcohols, nitrogen-containing heterocycles, etc. Using cheap and low-toxic acetone cyanohydrin as the cyanogen source, the efficient preparation of β-cyano ketone was achieved through the conjugate cyanation reaction of α,β-unsaturated carbonyl compounds. The influence factors such as the type and amount of base, temperature, solvent, and the amount of acetone cyanohydrin on the reaction were investigated. Results showed that the optimal experimental conditions were obtained as follows: LiOH·H2O was used as the base, the amount of substance ratio of reaction substrate, acetone cyanohydrin, and LiOH·H2O was 1:2.5:1.6, DMF and H2O in a volume ratio of 4:1 was used as solvent, and the reaction temperature was 60 °C. Under the optimal conditions, the highest yield of β-cyano ketone was 98%. Further investigation of the scope of substrates showed that the corresponding β-cyano ketones could be obtained from 16 chalcone derivatives in the yield of 85%~98%.