A controllable strategy to fabricate novel hierarchical V2O5/TiO2 nanofiber catalysts was proposed. The catalysts, which comprised primary TiO2 nanofibers and secondary V2O5 nanoparticles, were fabricated by combining electrospinning and hydrothermal growth. The controllable synthesis process and possible formation mechanism were also demonstrated through a series of time-dependent experiments. The hierarchical V2O5/TiO2 nanofiber catalysts were further applied in the oxidation of volatile organic compounds for the first time and were found to present a high oxidation performance for acetone. The morphological, structural, chemical characterization and catalytic performance analyses illustrated the highest catalytic activity was obtained from the synthesized V2O5/TiO2 nanofiber catalyst with 5 wt% V2O5. This finding could be attributed to the combined effect of the specific hierarchical nanofibrous morphology, abundant oxygen vacancies, and appropriate vanadium concentration.