In this work, an anti-biofouling polyvinyl chloride/zinc oxide (PVC/ZnO) membrane was prepared using the phase precipitation method for application in a University of Cape Town membrane bioreactor-submerged membrane bioreactor (UCT-MBR) for treatment of actual hospital wastewater. Effects of various ZnO nanoparticle (NPs) amounts (i.e. 0.1, 0.2, 0.3, and 0.4 g) on membrane properties were studied. The hypothesis of this effort was that ZnO would act as an anti-biofouling material, thus overcoming the formation of a bio-cake layer on the PVC-ZnO membrane surface, which in turn greatly extends the long-term of the membrane. The performance of the PVC membranes with ZnO-NPs in a submerged membrane bioreactor (SMBR) was systematically investigated. The characteristics of PVC/ZnO membranes were inspected via scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, and pollutant removal efficiency. It was found that the ZnO nanoparticles clearly influenced the structural morphology of the membranes. The addition of 0.1 g of ZnO nanoparticles resulted in a significant increase in the mean roughness by about 140%, with smaller mean pore size and narrow pore size distribution. The addition of ZnO nanoparticles, up to 0.3 g, had a positive effect on the hydrophilicity of the PVC/ZnO membrane with decreasing the contact angle (CA) value by 17.775 degrees. The pure water permeability (PWP) of the membrane improved by 315% with addition of 0.1 g of ZnO. The cake layer build-up on the membrane surface was reduced from 52.8 to 10.42 mu m with an increase of ZnO nanoparticles up to 0.3 g, as 0.4 g ZnO had no further effect on the cake layer thickness. The long-term of PVC-0.3 g NPs was improved up to 70 days before membrane cleaning compare with 29 days for neat PVC membrane. Chemical oxygen demand (COD) removal efficiency of UCT-MBR process was approximately similar and around 73.5% for all membranes.