The dot-matrix-initiated molecularly imprinted nanocomposite membranes (P/A-PTX@MIMs) with an anti-oil fouling layer have been successfully prepared. The multistage nanocomposite structure was carried out on P/A-PTX@MIMs for supplementing the anti-oil fouling property and the high specific recognition surface. (i) The proanthocyanidins (PC) was copolymerized with 3-aminopropyltriethoxysilane (APTEs) to generate functional nanoparticles layer in order to improve the anti-oil performance as well as to provide a second reaction platform for imprinted polymerization. (ii) The paclitaxel (PTX)-imprinted polymers were formed and distributed in an irregular dot-matrix-initiated multistage nanocomposite structure of the membrane by reformative sol–gel imprinted reaction. The static adsorption and dynamic adsorption presented that P/A-PTX@MIMs exhibited remarkable adsorption capacity, with the equilibrium adsorption capacity and adsorption time of 16.18 mg g⁻¹ and 60 min, respectively. Also, the impressive specific recognition capacity (α_{PTX/10-DBA III} = 4.10 and α_PTX/DOC = 3.67) and permselectivity (β_{10-DAB III/PTX} = 7.54, β_DOC/PTX = 7.72) with stable regeneration ability were obtained. The relationship between the structure and the performance was explored by analyzing the morphology and chemical structure, which included a detailed and in-depth study of the PTX-imprinted site formation and specific adsorption mechanisms. Importantly, the proposed modified strategy provided a potential “applicable strategy” in the chemical separation industry and biomedicine.