A robust fluorinated polyimide (FPI) nanofibers membrane was prepared by an electrospinning technique and subsequent thermo-crosslinking process. Compared to pristine FPI nanofibers membrane, the thermally crosslinked FPI nanofibers membrane possesses considerable mechanical strength (i.e., 31.7 MPa), small average pore size and narrow pore-size distribution and shows enhanced performance to prevent the growth and penetration of dendritic lithium, which is crucial to safe and reliable lithium-ion batteries. It is demonstrated that the FPI nanofibers membrane possesses admirable thermal stability and flame retardancy. The as-prepared pristine or thermally cross-linked FPI nanofibers membrane as a separator has greater electrolyte wettability, larger ionic conductivity, higher electrochemical oxidation limit, lower interfacial resistance, as compared to its non-fluorinated analogue nanofibers membrane and the commercial polyethylene (PE) separator. Moreover, compared with non-fluorinated PI analogue nanofibers membrane, the battery assembled with FPI nanofibers membrane with FPI binder exhibits enhanced cycle performance and rate capacity. And the electrochemical performances of the FPI-based battery are also better than the commercial battery fabricated by PE separator and polyvinylidene fluoride (PVDF) binder.