Cellulose acetate (CA) was used as a hydrophilic additive to blend with poly(vinylidene fluoride) (PVDF) for preparing casting solutions. A novel freeze and immersion precipitation coupling method was developed to improve the performance of PVDF microporous membranes. X-ray photoelectron spectroscopy (XPS) analysis confirmed the enrichment of CA segments on the PVDF membrane surfaces. The level of CA surface segregation on PVDF membrane surfaces was dramatically influenced by the freezing time. The hypothesis of solid (frozen DMSO)-liquid-solid (precipitated polymer) phase separation was proposed to explain the CA surface enrichment phenomenon. The mechanical strength and antifouling property of the PVDF microfiltration membranes were simultaneously improved by the synergistic action of freeze and immersion precipitation coupling technique. The PVDF microfiltration membranes exhibited higher permeability and better antifouling property in bioseparation process than that fabricated by the individual freeze technique.