Objective To establish an effective method for determination of synthetic cannabinoid JWH-122 by the high-performance liquid chromatography (HPLC), which is controled by China’s Regulations on non-clinical narcotic and psychoactive drug. Methods Methanol-deionized water (50%-50%) was used as mobile phase for gradient elution. In addition to the initial concentration in organic phase, gradient steepness, column temperature, flow rate and other chromatographic conditions, the determine wavelengths were tested so as to ifnd out optimal experimental conditions. Linearity range and speciifcity were tested under optimal conditions, and actual samples were used to verify the method established. Results Under the condition of ultraviolet spectrum detection wavelength at 221nm, initial concentration of 70%, organic phase gradient steepness of 0.5%/min, lfow rate at 1.2 ml/min and column temperature of 30℃,excellent linearity of JWH-122 was observed at 0.002mg/mL-0.1mg/mL and the detection limit (S/N≥3) was 0.1μg/mL. The test of actual samples suggested that JWH-122 was able to be well separated from the sample under the optimal conditions. Conclusion Our method has advantages of rapidity, sensitivity, accuracy and excellent separation efifciency, and is capable of the detection of synthetic cannabinoid JWH-122 of the novel “spice” drugs.