Separators significantly impact the safety and electrochemical properties of lithium-ion batteries (LIBs). However, the commonly used microporous polyolefin-based separators encounter inferior thermal stability and electrolyte wettability. Herein, a heat-resistant porous preoxidized polyacrylonitrile/ polyimide (OPAN/PI) composite nanofiber separator is successfully fabricated through synchronous thermal stabilization/imidization based on a polyacrylonitrile/polyamide acid (PAN/PAA) nanofiber membrane. The incorporation of PI significantly enhances the separator tensile strength by 79.89%, reaching 6.26 MPa. Furthermore, this hybrid separator exhibits splendid thermal dimensional stability (no shrinkage observed at 300 °C for 30 min) and flame-retardant performances, ensuring battery safety. The OPAN/PI separator demonstrates high porosity (78.4%), excellent electrolyte uptake (511.3%), and superior electrolyte wettability because of the intrinsic polar groups and porous structure, leading to enhanced ionic conductivity (1.853 mS/cm) and reduced interfacial resistance (188.4 Ω) compared to the Celgard separator. Furthermore, the LiFePO 4 /Li battery utilizing the OPAN/PI separator shows an admirable initial discharge specific capacity of 150.4 mAh g −1 and a surprising capacity retention ability of 101.0% after 100 cycles at 1C. Therefore, the OPAN/PI separator has great potential as an alternative separator for high-safety LIBs.