The interfacial polymerization (IP) of piperazine (PIP) and trimesoyl chloride (TMC) has been extensively utilized to synthesize the nanofiltration (NF) membrane. However, it is still a huge challenge to monitor the IP reaction, because of the fast reaction rate and the formed ultra-thin film. Herein, two effective strategies are applied to reduce the IP reaction rate: (1) the introduction of hydrophilic interlayers between the porous substrate and the formed polyamide layer; (2) the addition of macromolecular additives in the aqueous solution of PIP. As a result, in-situ FT-IR spectroscopy was firstly used to monitor the IP reaction of PIP/TMC reaction system, with hydrophilic interlayers or macromolecular additives. Moreover, we study the formed polyamide layer growth on the substrate, in a real-time manner. The in-situ FT-IR experimental results confirm that the IP reaction rates are effectively suppressed and the formed polyamide thickness reduces from 138±24 nm to 46±2 nm. Furthermore, the optimized NF membrane with excellent performance are consequently obtained, which include the boosted water permeation flux about 141~238 (L·m2·h/MPa) and superior salt rejection of Na2SO4 > 98.4%.