Separating the natural product of paclitaxel from its structural analogs still remains a significant challenge. In this work, a novel molecular imprinting membrane (Cell/SiO2-MIM) with specific recognition sites was hierarchically constructed for paclitaxel (PTX) separation. Inspired by mussel, inorganic silica nanoparticles (SiO2 NPs) were introduced onto the surface of the regenerated cellulose membrane as polymerization platform in an attempt to enhance the permeation flux of the membrane. The specific recognition sites of PTX were constructed on the nanoscale silica surface through the bulk polymerization of vinylpyridine in the presence of PTX as templates, leading to the membrane with the selective recognition ability for the target molecule (PTX). The as-synthesized imprinting membrane exhibited excellent selective adsorption capacity and perm-selectivity towards PTX, with the maximum adsorption amount and separation factor of 46.36 mg/g and 3.77, respectively. Moreover, after six consecutive adsorption and desorption cycles, the membrane maintained the excellent stability and reusability, which facilities its potential application in an industrial scale.