The development of a stable structure separation membrane with adaptive switching wettability has positive significance for the expansion of membrane applications, especially in complex processing scenarios. Herein, a kind of core-shell cellulose acetate/silicon dioxide (CA/SiO2) hybrid nanofiber membrane with a semi-interpenetrating structure and switching wettability surface property was prepared via electrospinning process and subsequently in-situ hydrolysis, which integrated a superamphiphilicity SiO2 shell onto the porous CA nanofibers core to form an anchor embedding structure by vacuum forcing the silica precursor into the pores of CA nanofibers. The obtained CA/SiO2 hybrid nanofiber membrane exhibited superamphiphilicity in air with adaptive switching wettability, appearing non-stick to oil underwater or to water underoil, corresponded to superoleophobicity underwater and superhydrophobicity underoil, respectively. The CA/SiO2 hybrid nanofiber membrane with the hydrolysis time of 5 h demonstrated excellent properties. It achieved permeation fluxes of 19771 and 9104 L/m2·h with a separation efficiency exceeding 99.99% for immiscible light/heavy oil/water mixtures when pre-wetted by water and oil and subjected to gravity. Moreover, the semi-interpenetrating structure of SiO2 nanoparticles to CA nanofibers ensured the structural stability of the CA/SiO2 hybrid nanofiber membranes, which endowed it with excellent reusable performance.