It is a great challenge to achieve robustly bonded, fully covered, and nanoscaled coating on the surface of electrospun nanofibers. Herein, we develop a controllable, facile, and versatile strategy to in-situ grow superlubricated nano-skin (SLNS) on the single electrospun nanofiber. Specifically, zwitterionic polymer chains are generated from the nanofiber subsurface in an inside-out way, which consequently form a robust network interpenetrating with the polymeric chains of the nanofiber matrix. The nanofibers with SLNS are superlubricated with the coefficient of friction (COF) lower than 0.025, which is about 16-fold of reduction than the original nanofibers. The time-COF plot is very stable after 12, 000 cycles of friction test, and no abrasion is observed. Additionally, the developed nanofibrous membranes possess favorable tensile property and biocompatibility. Furthermore, the nanofibrous membranes with SLNS achieve prevention of post-operative adhesion, which is confirmed in both rat tendon adhesion model and abdominal adhesion model. Compared with clinically-used antiadhesive membranes such as Interceed and DK-film, our nanofibrous membranes are not only more effective but also have the advantage of lower production cost. Therefore, this study demonstrates a potential of the superlubricated nanofibrous membranes in-situ grown based on a SLNS strategy for achieving prevention of post-operative adhesion in clinics. Post-operative adhesions are a major complication from surgical intervention. Here, the authors develop a technique to grow a super-lubricating layer over electrospun nanofibers which was demonstrated to prevent postoperative adhesions with better outcomes than commercial products when compared in two in vivo models.