As a pivotal part of lithium-ion batteries, separator is supposed to have high strength, thermal stability and excellent wettability. In this study, polyformaldehyde/cellulose nanofibers blend separators are firstly prepared via thermally induced phase separation to improve the performance, especially the safety of LIBs. The polyformaldehyde/cellulose blend separators show considerable tensile strength (116 MPa) and Young's modulus (6.07 GPa) owing to the high crystallinity and high performance of polyformaldehyde and cellulose. In particular, benefiting from their abundant polar groups and highly porous structure, the polyformaldehyde/cellulose blend separators possess high electrolyte uptake (412%) and small contact angle (19°) as compare to the commercial polyethylene separator (115%, 58°). Moreover, the thermal treatment tests indicate that the polyformaldehyde/cellulose blend separators are thermally stable at as high temperature as 180 °C. And the polyformaldehyde/cellulose blend separators show higher ionic conductivity (1.39 mS cm−1) and lower interface resistance (49.5 Ω) than polyethylene separator (0.76 mS cm−1, 136.4Ω). As expected, the LiFePO4/Li cell with polyformaldehyde-20-cellulose blend separators exhibit the best stable cycling performance and improved rate performance than PE separator, especially at high rate. In summary, the polyformaldehyde/cellulose blend separators are promising new kind of separator for LIBs with high safety and enhanced performance.