The aim of the present study was to consider quercetin and benzophenone mutual interaction in methanol solution under continuous UV-B irradiation. Following the UV-B induced changes by HPLC chromatography, the obtained results revealed significant acceleration of quercetin degradation in the presence of benzophenone. An unambiguous identification of quercetin degradation products was enabled by direct FI-ESI-MS analysis. The presence of benzophenone did not just accelerate but also changed the mechanism of quercetin degradation. Irradiation of quercetin in the absence of benzophenone led to the formation of the solvent-addition product 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dimetoxy-2,3-dihydro-4H-chromen-4-one. The products obtained in the presence of benzophenone, formed as the result of C-ring opening, were identified as 3,5-dihydroxy-2-[methoxy(oxo)acetyl]phenyl 3,4-dihydroxybenzoate and methyl-oxo(2,4,6-trihydroxyphenyl)acetate.