Low-fouling thin-layer hydrogel composite membranes were prepared during UV initiated grafting from of the hydrophilic monomer poly(ethylene glycol) methacrylate onto polyethersulfone (PES) ultrafiltration (UP) membranes. The selectivity of the functionalized membranes was adjusted by varying the UV irradiation dose and applying the cross-linking agent N,N'-methylene bisacrylamide. Virgin and composite membranes were tested in short (20-fold volume reduction) and long (24 h) dead-end (DE) filtration experiments of various protein solutions and the performance improvement by the membrane hydrophilization was evaluated. Moreover, the effects of membrane molecular weight cutoff, solute size, and solute charge (as function of pH) as well as cleaning were evaluated. The dominating fouling mechanisms were identified using the classical model equation proposed by Hermia [Hermia, J. Constant Pressure Blocking Filtration Laws-Application to Power Law Non-Newtonian Fluids. Trans. Inst. Chem. Eng. 1982, 60, 183] for DE filtration mode. The results showed that the surface functionalization improved the membrane performance during filtration of protein solutions. Moreover, the cleanability of functionalized membranes with water was much more effective compared to unmodified PES membranes. The performed fouling mechanism study clarified the occurring processes during filtrations with virgin and composite membranes.