Interfacial polymerized thin-film composite (TFC) membranes have been widely investigated for molecule separation and water purification. While the support is limited to the hydrophilic micro and/or mesoporous support with concentration polarization, which may compromise the separation efficiency. Here, a copper hydroxide nanostrands (CHNs) assisted interfacial polymerization process was developed to form ultrathin hydrophilic polyamide (PA) films on macroporous and hydrophobic polytetrafluoroethylene (PTFE) substrates by confining the m-phenylenediamine (MPD) aqueous solution in the preformed CHNs networks on the PTFE substrate. The porous hydrophilic CHNs serve as the micro-reservoir for amine aqueous solution, smooth and seal the macroporous PTFE substrate, and confine the interfacial polymerization closely on their surface. The thickness of the top PA layer could be easily controlled by the thickness of the CHNs layer. The resulted Janus PA/PTFE TFC membrane with 102nm thick PA selective layer demonstrates 93% rejection for Rhodamine B (molecular weight 479) with a permeance of 420Lm−2h−1bar−1 in industrial preferred cross-flow module. This performance is one order higher than that of the commercial membranes with similar rejections. The newly developed PA/PTFE TFC membrane holds a widely application in separation and purification of small molecules.