Traditional polyamide nanofiltration membranes often can't obtain ideal ion selectivity due to their wide pore size distribution. In this work, a β-cyclodextrin modified sodium hyaluronate (HA-CD) was introduced to achieve the dragging effect of piperazine by non-specific hydrogen bond interaction between HA-CD and substrate and piperazine, thus realizing the purpose of sustained release of piperazine. The MD simulation results demonstrated that the diffusion rate of piperazine was reduced by approximately two orders of magnitude due to the interaction effect. In addition to making the polyamide layer thinner and smoother, HA-CD also narrows the pore size distribution. The salt filtration test showed that the prepared membrane has excellent anion selectivity (αmax:114) and permeability (10.66 L m−2 h−1 bar−1). Long-term filtration and nano-scratch test results demonstrated that the prepared membranes have good operational stability (the permeability only decreased about 30%) and mechanical strength (the interface bonding strength increased about 270%). By exploring the effect of the interaction between HA-CD and substrate and piperazine on the interfacial polymerization process, which proved the feasibility of realizing high permeability selectivity and stability of the membrane by constructing the functional bridge between substrates and aqueous monomers.