The regulation of interfacial polymerization (IP) is the critical procedure for the preparation and industrialization of thin film composite (TFC) nanofiltration (NF) membranes. However, the IP control is still a huge challenge based on the extremely rapid reaction rate during the fabrication of the membrane. Herein, a new strategy was developed to modulate the IP process to increase the NF membrane performance. The aldehyde oxidized dextran (ODex) interlayer was deposited on the polysulfone ultrafiltration substrate, and the enamine would form between the secondary amines of aqueous phase monomer piperazine (PIP) and aldehyde groups of the ODex. Based on the by-products of IP, the enamine gradually decomposed reversibly in a hydrogen ion environment and the immobilized PIP was released and continued to react with organic phase monomer trimesoyl chloride (TMC). Accordingly, a thinner and exhibiting nanowire structures separation layer with fewer defects was obtained. The permeance of the optimal NF membrane with 0.7 wt% ODex interlayer deposition concentration could reach up to 208 ± 10.4 Lm⁻²h⁻¹MPa⁻¹, which was more than 2.5 times permeance of the ordinary NF membrane, and the rejection rate for Na₂SO₄ could reach 99.3 ± 0.3%. In addition, the mono- and divalent ion selectivity of the modified membrane was also greatly improved (α_NaCl/Na2SO4 = 115). This study provides a new idea for the regulation of IP process, thereby suggesting a reasonable proposal for improving the performance of TFC NF membranes.