Separators in Li-ion batteries are crucial components that have a great impact on battery safety and lifespan. The design of multifunctional separators is desired to tackle problems, such as thermal runaway or electrode degradation. However, addressing both of these challenges is hardly achievable. Here, we propose a versatile process to form hybrid separators with a tunable architecture and surface chemistry. Combining electrospinning with sol−gel chemistry, homogeneous nanofibers made of poly(vinylidene fluoride-co-hexafluoropropylene) and up to 37 wt % of silica were obtained, showing high mechanical properties and outstanding thermal stability. Multilayer separators were designed to achieve shutdown properties: outer layers of hybrid fibers maintained the dimensional stability of the separator, while an inner layer of polymer fibers melted to raise the ionic resistance. Notably, in the battery cell configuration, we demonstrate the advantages of incorporating hybrid fibers, which help maintain the dimensional stability of the separator. The hybrid nanofibers were also functionalized with amine or lithium sulfonate groups to trap hydrofluoric acid (HF) or metallic cations. XPS analyses revealed the protonation of amine functions on separator fibers after cycling in LiNiO2||graphite coin cells, which evidenced the scavenging of acidic species such as HF. In addition, we observed a correlation between the amount of Ni cations deposited on the graphite after cycling and the capacity loss attributed to the graphite electrode. The functional separator incorporating terpyridine molecules allowed for a reduced nickel crossover from LiNiO2 to graphite and better capacity retention compared with the other separators.