A solid-phase extraction method for the efficient analysis of the excretion-dynamics of flavonoids in urine was established and described. In this work, in situ surface radical chain-transfer polymerization and in situ anion exchange were utilized to tune the extraction performance of poly(1-vinyl-3-hexylimidazolium bromide)-graphene oxide-grafted silica (poly(VHIm⁺Br⁻)@GO@Sil). Graphene oxide (GO) was first coated onto the silica using a layer-by-layer fabrication method, and then the anion of poly(VHIm⁺Br⁻)@GO@Sil was changed into hexafluorophosphate (PF₆⁻) by in situ anion exchange. The interaction energies between two PILs and four flavonoids were calculated with the Gaussian09 suite of programs. A Box-Behnken design was used for the optimization of four greatly influential parameters after single-factor experiments to obtain more accurate and precise results. Coupled to high performance liquid chromatography, the poly(VHIm⁺PF₆⁻)@GO@Sil method showed acceptable extraction recoveries for the four flavonoids, with limits of detection in the range of 0.1–0.5 μg L⁻¹, and wide linear ranges with correlation coefficients (R) ranging from 0.9935 to 0.9987. Under the optimum conditions, the proposed method was applied to analyze the urines collected from a healthy volunteer. The excretion amount-time profiles revealed that 4–15 h was the main excretion time for the detected flavonoids. The results indicated that the newly developed method offered the advantages of being feasible, green and cost-effective, and could be successfully applied to the extraction and enrichment of flavonoids in human body systems allowing the study of the metabolic kinetics.