Thirteen flavonoids (quercetin, morin, myricetin, luteolin, fisetin, kaempferol, galangin, apigenin, chrysin, EC, ECG, EGC and EGCG) were used to investigate their main antioxidant mechanism as well as structure-activity relationship by quantum chemical calculation and verifying by the in vitro typical antioxidant assays (DPPH, ABTS and FRAP). The reaction enthalpies related to three possible ... [Show full abstract] radical-scavenging mechanisms were calculated by the density functional theory (DFT) M06-2X method. Both in ethanol and acetone, the bond dissociation enthalpy (BDE) was much lower than ionization enthalpy and proton affinity values, and the BDE rank of 13 flavonoids was similar to that of their antioxidant activity determined by the in vitro trials. It was revealed that flavonoids thermodynamically preferred HAT mechanism in polar media. The number and position of phenolic hydroxyl showed great influences on the antioxidant activity of flavonoids, and the flavonoids possessing both of C3 hydroxyl group and catechol moiety exhibited stronger antioxidant activity than which with one or none of them.