Abstract: In order to improve the economic value of industrial hemp, an active ingredient cannabinoid (CBD) with medicinal value from industrial hemp leaves was extracted by ionic liquid assisted ultrasonic method and the extraction process was optimized. In this study, C₈mimNTF₂ was selected as the best extraction solvent from 16 kinds of imidazole ionic liquids based on the yield of CBD. Then single factor experiment was conducted on six factors affecting the yield of CBD extraction by ionic liquid assisted ultrasonic method. The six factors included: Ultrasonic power, ultrasonic temperature, ultrasonic time, ethanol concentration, molar concentration of ionic liquid and liquid material ratio. And the ethanol concentration was 65%. The ionic liquid molar concentration was 0.3 mol/L (65% ethanol solution preparation). On the basis of these results, four significant factors (ultrasonic power, ultrasonic temperature, ultrasonic time and liquid material ratio) were screened out by Plackett-Burman experimental design. The extraction process was further optimized by response surface Box-Behnken experimental design. The optimum extraction process conditions of CBD significant factors were as follows: Ultrasonic power 280 W, ultrasonic temperature 50 ℃, ultrasonic time 62.5 min, liquid material ratio 25 mL/g. Under the above conditions, the yield of CBD extracted by ionic liquid C₈mimNTF₂ was 7.66%±0.2%, the yield of CBD extracted by methanol was 6.42%±0.3%, and the yield of CBD extracted by 65% ethanol solution was 5.81%±0.2%. The extraction ability of CBD was ionic liquid C₈mimNTF₂>methanol>65% ethanol solution. The CBD degradation experiment showed that the CBD degradation rate of ionic liquid C₈mimNTF₂ was 16.40%±0.3%, which was smaller than that of methanol (24.65%±0.6%) and 65% ethanol solution (32.88%±0.5%). The results showed that adding 65% ethanol solution into ionic liquid C₈mimNTF₂ could not only reduce the degradation rate of CBD, but also increase the yield of CBD. This study proved that ionic liquid was not only a protective agent for CBD, but also an excellent solvent for CBD extraction. The technology of extracting CBD by ionic liquid assisted ultrasonic method was developed, which provided data support for the development and utilization of industrial hemp CBD.