Hollow fiber membrane (HFM) is widely used for extracorporeal membrane oxygenator (ECMO) because of large membrane area, high packing density, self-supporting structure and good flexibility. However, polymeric HFMs often suffer from a trade-off between gas permeability and anti-plasma leakage performance. In this study, HFMs with gradient structure were prepared by introducing COF-42 as fillers into the polypropylene (PP) matrix through surface segregation. The enriched COF-42 near the upper surface endowed the membrane a gradient structure to reduce the plasma leakage and improve gas permeability. Compared with PP membranes, PP/COF-42 oxygenation membranes retained good blood compatibility and higher mechanical properties. The PP/COF-42–0.5 HFMs exhibited O2 exchange rate of ∼ 342.6 ml min−1 m−2 and CO2 exchange rate of ∼ 989.6 ml min−1 m−2, which was about 218.7 % and 15.4 % larger than that of the PP HFMs, respectively. Moreover, the simulated plasma leakage time could reach 124 h, which was about 21 times longer than that of PP HFMs. The membranes exhibited excellent blood oxygenation performance and anti-plasma leakage performance, which had great potential in ECMO.