Abstract: The objective of this study was to optimize the extraction process of total flavonoids from Haloragis micrantha (Thunb.) R. Brown. and explore its antioxidant activity. With the yield of total flavonoids as an evaluation index, single factor tests were used to investigate the effects of ethanol volume fraction, solid-liquid ratio, ultrasonic temperature and extraction time on the total flavonoids content of Haloragis micrantha (Thunb.) R. Brown., and the Box-Behnken method was used to optimize the extraction process. The scavenging ability and total reducing power of total flavonoids of Haloragis micrantha (Thunb.) R. Brown. to DPPH and ABTS⁺ free radicals were detected. The results showed that optimum extraction process was ethanol volume fraction of 76.15%, liquid to material ratio of 1:39.66 g/mL, ultrasonic time of 41.14 min. The yield of total flavonoids from Haloragis micrantha (Thunb.) R. Brown. was 28.61±0.05 mg/g. The total flavonoids of Haloragis micrantha (Thunb.) R. Brown. could effectively scavenge DPPH and ABTS⁺ free radicals. Within a certain range, the scavenging ability increased with the increasing of mass concentration, and the total flavonoids of Haloragis micrantha (Thunb.) R. Brown. had high reducing power and better antioxidant activity. The total flavonoids of Haloragis micrantha (Thunb.) R. Brown. had the strongest ability to scavenge ABTS⁺ free radicals. When the concentration of total flavonoids was 3 mg/mL, the clearance rate of ABTS⁺ were 98.28%, which was equivalent to 3 mg/mL vitamin C (clearance rate was 99.81%). This process would be simple and feasible, and the extracted total flavonoids have good antioxidant activity.