Loose nanofiltration membranes (LNF) have wide applications in the field of precise separation of small organic molecules. However, high separation precision of organic molecules with salts and a high water flux are still the challenges in the commercial applications of LNF membranes. In the current work, polyethersulfone (PES)/hydroxylated polyethersulfone (PES-OH) LNF membranes were synthesized by nonsolvent-induced phase separation (NIPS) based on reactive porogen (butyl dicarbonate, BDC) for the first time. The reactive porogen was decomposed to produce nanobubbles during heat-treated casting solution and phase inversion in HCl coagulation. It was found that the heat-treatment temperature of the casting solution was higher, the viscosity of the solution at 20 °C was higher due to the existence of more nanobubbles from BDC decomposition in the casting solution. Moreover, heat-treatment temperature had decisive impacts on the structure and separation property of the formed LNF membranes as nanobubbles actually acted as pore-forming agents. The HCl coagulation/immersion baths also promoted the BDC decomposition to produce the nanobubbles and improved the transmembrane water flux without sacrificing rejection and separation precision performance. The synthesized LNF membrane had a pore diameter approximately 3.81 nm, with a flux up to 200.2 L·m−2·h−1. Direct Black 38 shows a rejection of > 99 %, whereas NaCl shows a rejection of < 5 %, exhibiting a good separation accuracy and found superior to the separation performance in the literature. This research result has offered a novel approach for the preparation of superior performance LNF membranes, which can be utilized for precise separation.