Response surface methodology was used to optimize the extraction processing of the total flavonoids in the seed of tartary buckwheat according to central composite design principle based on the single factor experimental results. Through the analysis of cross-interaction among factors by the Design-Expert software, the optimal extraction conditions were found to be liquid-material ratio 20∶1, alcohol concentration 75%, extraction temperature 70℃, and extraction time 4h. The extraction rate of flavonoids was 2.632% under the optimal extraction conditions. Meanwhile, the antioxidant activity of total flavonoids was assessed by scavenging hydroxyl radicals and DPPH radical, anti-lipid peroxidation, and reducing power. The results showed that the total flavonoids in the seed of tartary buckwheat presented a strong antioxidant activity to scavenge DPPH radicals and IC₅₀ values of anti-lipid peroxidation, scavenge hydroxyl radicals, and DPPH radical were 1.115,0.498, and 2.235μg/mL.