In order to optimize the extraction conditions of continentalic acid, the main compound from Aralia continentalis root, we developed a model using the response surface methodology. The continentalic acid yield was analyzed and quantified by high-performance liquid chromatography coupled with UV detection. The extraction solvent, temperature, and time the three main factors for ultrasound-assisted extraction were optimized using the central composite design. Analysis of variance showed a good model fit (R2 = 0.9323). The maximum extraction of continentalic acid obtained experimentally was 1.0138 % under an extraction temperature of 33 °C and extraction time of 28 min when 100 % ethanol was used as the solvent. The experimental value was in good agreement (the yield 1.0103 %) with those predicted values. The results clearly showed that quality by statistical design could be effectively applied to optimize extraction of continentalic acid.