In this study, crosslinked chitosan resin grafted by quercetin (QCCR) was used as a novel adsorbent to separate flavonoids. Functional quercetin groups were introduced to the adsorbent matrix, and the hydrophobic interaction occurred when these functional groups in the adsorbent approached the adsorbate with the same ring structure, which enhanced the adsorption selectivity towards flavonoids. The hydrophobic interaction played an important role in the selective adsorption. Atomic force microscopy provided intuitively the spatial conformation and the interactions between flavonoids and QCCR at the molecular level. The influences of functional groups of synthesized adsorbents on the adsorption selectivity and the optimum conditions were investigated in detail. QCCR was considered as an alternative material for obtaining the bioactive flavonoid compounds with high concentration.