In this work, the atomic layer deposition-zinc oxide (ALD-ZnO) modified membrane was fabricated and the effects of ionic strength, co-existing Ca2+ and Mg2+ on its fouling potential were systematically investigated. Results showed excellent anti-irreversible fouling performance of PVDF-ZnO modified membrane with co-existing cations. Attractively, the values of declined membrane flux dropped by 25.7%, 25.9% and 22.3% after ZnO modification in the presence of 50 mM NaCl, 1.0 mM Ca2+ and 1.0 mM Mg2+, respectively. Besides, Ca2+ was prone to cause membrane fouling than Mg2+. Furthermore, fitting of multistage filtration models revealed that membrane fouling was ascribed to dynamic adsorption initially, followed by surface and pores deposition when filtrating BSA with or without Mg2+. However, the modified membrane experienced reverse process with higher ionic strength or Ca2+ addition due to BSA molecular cluster. Moreover, the reduced repulsive energy induced by charge screening and calcium bridging resulted in slight aggravation of membrane fouling. Interestingly, the flux of PVDF-ZnO fouled membrane was easily recovered after physical cleaning. These findings provided deep insight into practical application of ALD modified membrane in wastewater remediation.