Objective Response surface methodology ( RSM ) was applied to optimize the ultrasonic extraction conditions for flavonoids from Coreopsis tinctoria Nutt. Methods The influence factors of ultrasonic extraction were evaluated using the Box-Behnken central component experiments and analyzed by RSM. Results The optimum extraction conditions were confirmed as follows:extraction time 30. 0 min, ratio of liquid to solid 21∶1, concentration of ethanol 60%. The yield of flavonoids under this condition was (4.65±0.036)% (n=3). Conclusion The flavonoids could be extracted with stability and higher yield from Coreopsis tinctoria Nutt under optimized conditions.