Abstract: To optimize the extraction conditions of flavonoids from Lycium ruthenicum by Plackett-Burnman combined with response surface methodology and evaluate its antioxidant activity. The factors with significant influence and response surface center were determined by investigating the effects of five factors on extraction rate based on Plackett-Burnman design test and the steepest ascent serach experiment. Meanwhile, the extraction technology was optimized by Box-Behnken response surface methodology. The antioxidant activity of flavonoids from Lycium ruthenicum Murr. was evaluated by using FRAP, ABTS and DPPH, which was then compared with that of ascorbic acid in parallel. Results indicated that the optimized process conditions were as follows: Ethanol volume fraction 51%, liquid to solid ratio 30:1, extraction temperature 62 ℃, extraction time 42 min, ultrasonic power 240 W, the extraction rate was up to 42.0974 mg/g(raw material) and the RSD with the theoretical value was 3.24%. The antioxidant activity tests revealed that the ferric reducing capacity of flavonoids from Lycium ruthenicum Murr. was stronger than that of ascorbic acid, the IC₅₀of ABTS and DPPH radical scavenging activities of Lycium ruthenicum Murr. flavonoids were 0.0252 and 0.0272 mg/mL, respectively, which were higher than those of ascorbic acid, and the antioxidant activity of flavonoids followed a dose-dependent manner at all the tested concentrations. This study would provide a theoretical basis for the further development of Lycium ruthenicum Murr. resources and the extension its industrial production chain.