Nanofiltration membranes bearing high separation and anti-fouling performances represent an efficient separation technology for desalination applications. Although porous organic frameworks (POFs) are considered as a promising candidate for constructing membranes with improved water flux due to their unique advantages such as well-defined pores and tunable functionality, there is still challenge for anti-fouling property of the membranes. Zwitterions possessing balanced charge groups are very attractive for preparing anti-fouling membranes owe to their high hydration capacity. In this study, nanocomposite membranes were prepared by embedding the zwitterionic functionalized “cage-like” POFs (Z-PAF-C) into polyamide (PA) layer. The POFs blended within polymeric membranes could provide more and shorter channels for water molecules through the hybrid membranes, attributing to the novel porous structure of POFs. The zwitterionic groups derived from Z-PAF-C could enhance the hydrophilicity of membrane surface, rendering the membranes promising anti-fouling properties. The water flux of the membrane was increased distinctly from 24 L m−2 h−1 to 42.6 L m−2 h−1 under 0.2 MPa with the loading of Z-PAF-C ranged from 0 g/m2 to 0.85 g/m2 while the retention for Na2SO4 (1 g/L) was maintained at 90.6%. This study demonstrated that the introduction of the zwitterionic functionalized POFs can improve the hydrophilicity and charge negativity of membrane surface, resulting in an enhanced water flux and anti-fouling property.