A novel strategy is developed to synthesize prussian blue nanocubes/hollow polypyrrole (PB/H-PPy) nanocomposites for enhanced electrochemical determination of hydrogen peroxide (H2O2). PB/H-PPy nanocomposites were prepared through a facile approach, where Fe3O4 spheres acted as both the template and source of Fe3+. It was found that the dissolving of Fe3O4 in an acidic environment not only led to the successful formation of a hollow structure of PPy but also provided Fe3+ and assisted the formation of PB around H-PPy, therefore leading to the formation of PB/H-PPy. The morphology, structure, and electrochemical properties of PB/H-PPy were characterized by transmission electron microscopy, field-emitting scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical techniques. The results indicated that a large number of PB nanocubes were densely distributed on the surface of H-PPy. Meanwhile, the combination of PB with H-PPy made the sensor based on PB/H-PPy exhibit an excellent performance toward H2O2 detection with a wide linear range of 5.0 mu M to 2.775 mM, a high sensitivity of 484.4 mu A mM(-1) cm(-2), and a low detection limit of 1.6 mu M (S/N = 3). This work provided a new approach for the rational design and fabrication of an electrocatalytic material with improved catalytic activity.