Structural design of photocatalysts is of great technological importance for practical applications. A rational design of architecture can not only promote the synthetic performance of photocatalysts but also bring convenience in their application procedure. Nanofibers have been established as one of the most ideal architectures of photocatalysts. However, simultaneous optimization of the photocatalytic efficiency, mechanical strength, and thermal/chemical tolerance of nanofibrous photocatalysts remains a big challenge. Here, we demonstrate a novel design of TiO2-SiO2 composite fiber as an efficient photocatalyst with excellent synthetic performance. Core-shell mesoporous SiO2 fiber with high flexibility was employed as the backbone for supporting ultrasmall TiO2 nanowhiskers of the anatase phase, constructing core@double-shell fiber with luffa-sponge-like appearance. Benefitting from their continuously long fibrous morphology, highly porous structure, and completely inorganic nature, the TiO2-SiO2 composite fibers simultaneously possess high photocatalytic reactivity, good flexibility, and excellent thermal and chemical stability. This novel architecture of TiO2-SiO2 glass composite fiber may find extensive use in the environment remediation applications.