Background: Inula helenium, which belongs to thecomposite family, is an important crude drug in traditional Chinese medicine. Materials and Methods: The effects of ethanol concentration, liquid to solid ratio, extraction temperature, and duration of microwave irradiation on the flavonoid extraction yield were studied through a single-factor experiment. An orthogonal array (L 9 (3 4 )) was then constructed to achieve the best extraction conditions. Results: Variance analysis revealed that ethanol concentration significantly affected the extraction yield. The optimal conditions were as follows: ethanol concentration, 50% (v/v); liquid to solid ratio, 15:1; duration of microwave irradiation, 240 s; and extraction temperature, 60°C. Conclusion: Under these optimal conditions, the total flavonoid yield was 18.34 ± 0.64 mg/g. The use of a microwave-assisted process dramatically reduced the time needed for extraction of flavonoids from I. helenium.