Radiolysis of the flavonol quercetin, a natural antioxidant, was performed in methanol. The degradation process was followed by HPLC analyses. The major product was identified as a depside (Q1) by NMR and LC-MS. The G(Q1) radiolytic factor was plotted versus the initial concentration of quercetin. This radiolytic process was attributed to the CH3O* radicals presented in the irradiated medium. The proposed mechanism invoked a stereospecific oxidation of the 3-hydroxyl group of quercetin which led to C-ring opening and to the formation of the depside Q1. In presence of water, Q1 was transformed into another depside, Q2, by an inverse esterification reaction. A chemical equilibrium was observed between Q1 and Q2. The comprehension of the radiolytic process of quercetin in methanol solution is of importance. Indeed, the same type of oxidative reactions could occur on flavonoids during preservation of food by ionizing radiation.