This study explores the physicochemical characteristics of an innovative mixed matrix membrane made from polyethersulfone (PES) and hollow Zein nanoparticles (HZNs), which are derived from the corn storage protein, Zein. HZNs, with a mean diameter of 40 nm, were applied to address the challenges associated with metal and inorganic nanoparticles, such as their tendency to accumulate unevenly on the membrane surface. The membranes were fabricated by incorporating varying concentrations of HZNs into the PES casting solution through the nonsolvent phase separation method. The addition of HZNs enhanced the hydrophilicity and pure water flux of the membranes. It also modified the membrane structure, morphology, pore size, molecular weight cut-off (MWCO), and porosity. Increasing the HZN concentration up to 5 wt% proportionally improved the surface hydrophilicity and roughness of the membranes. Furthermore, the modified membranes exhibited excellent performance in rejecting heavy metals at an acidic pH of 4, with the 5 %-HZNs/PES membrane achieving a 100 % rejection rate without significantly affecting water flux due to Donnan exclusion. Additionally, the 5 %-HZNs/PES membrane showed a minimal irreversible fouling resistance (Rir) of 17.9 % and a fouling resistance ratio (FRR) of 82.1 %. These results indicate that the developed mixed matrix membrane holds significant promise for applications in water purification processes.