The UF membrane with a narrow and uniform pore size distribution and a low tendency to foul has significant applications in wastewater treatment. A major hindrance in the preparation of the UF membrane with these features is the lack of a scalable and economical membrane fabrication method. Herein, we devise a new strategy to prepare a high-quality polyvinylidene fluoride/polymethyl acrylate/cellulose acetate (PVDF/PMMA/CA) blend UF membrane via a combination of the etching mechanism with the traditional Loeb–Sourirajan (L-S) phase inversion method. Different concentrations of silicon dioxide (SiO2) nanoparticles (NP) in the membrane matrix were etched by using a 0.2 M hydrofluoric acid (HF) solution in a coagulation bath. This strategy provided the membrane with unique features along with a narrow and uniform pore size distribution (0.030 ± 0.005 μm). The etched membrane exhibits an increase of 2.3 times in pure water flux (PWF) and of 6.5 times in permeate flux(PF), with a slight decrease in rejection ratio (93.2% vs. 97%) when compared to than that of the un-etched membrane. Moreover, this membrane displayed outstanding antifouling ability, i.e., a flux recovery ratio (FRR) of 97% for 1000 mg/L bovine serum albumin (BSA) solution, a low irreversible fouling ratio of 0.5%, and highly enhanced hydrophilicity due to the formation of pores/voids throughout the membrane structure. The aforementioned features of the etched membrane indicate that the proposed method of etching SiO2 NP in membrane matrix has a great potential to improve the structure and separation efficiency of a PVDF/PMMA/CA blend membrane.