Enzymatic membrane bioreactors (EMBRs), endowed with synergistic catalysis-separation performances, have in recent decades shown enormous potential for practical applications. Conventionally, membrane properties and operating parameters play important roles in catalysis-separation processes of these complicated and large-scale systems. Therefore, to achieve higher catalytic and filtration efficiencies, hollow fiber polysulfone microfiltration membranes with a perfect radial gradient of pores were selected as substrates, and the subsequent enzyme-immobilization process was achieved in a facile way by pressure-driven filtration and crosslinking, to finally construct an enhanced EMBR system. Lipase from Candida rugosa was introduced as the functional enzyme and was crosslinked by glutaraldehyde (GA), with the catalytic hydrolysis of glycerol triacetate used as the model reaction. The performances of these designed EMBR systems were evaluated using the response surface methodology to optimize various operating parameters by testing substrate concentrations from 0.05–0.2 M, membrane fluxes from 102.6–287.4 L m⁻² h⁻¹, reaction pH values from 5.5–8.5, and temperatures from 25–55 °C. Corresponding association models were then established according to EMBR performances to obtain R² values of 96.69% and 97.27% respectively. The complete EMBR system showed an excellent performance of around 0.178 mmol min⁻¹ g⁻¹ under optimum operating conditions, and showed marked improvement in the stability and membrane activity of the EMBR after microfiltration and crosslinking. This simple and low-cost approach to fabricate a high-performance EMBR has great potential for applications in various industrial-scale lipase-catalyzed reactions.