Hollow CuO nanospheres have been prepared via a reduction reaction of copper ions on porous Si nanowires combined with calcination in air and uniformly anchored on their surfaces. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were employed to characterize and analyze as-synthesized samples. The results reveal that Si nanowires fabricated from heavily doped Si wafer are formed with a meso-porous structure by an Ag-assisted etching approach, and Cu nanoparticles are formed and uniformly decorated on the Si nanowires through a reaction of copper ions reduced by silicon. After annealing in air, Cu nanoparticles are in situ oxidized and transformed into CuO, leading to the formation of hollow nanospheres because of the Kirkendall effect. The diameter size of as-prepared CuO hollow spheres anchored on porous Si nanowires is mainly around 30 nm. Finally, in order to illuminate the advantages of this novel hybrid nanostructure of nanosized hollow spheres supported on porous nanowires, its electrochemical sensing performance to hydrazine as an example has been further investigated. The results confirm that it is a good potential application to detect hydrazine.