In this paper, hollow hematite nano-polyhedrons (Fe-HNPs) were synthesized via a facile solution route. The abundance of high indexed facets was demonstrated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. A new electrochemical biosensor for nitrite determination was then proposed by using the hematite hollow nanopolyhedron as the sensing layer. Electrochemical tests showed that the Fe-HNPs could act as efficient enzyme-like electron mediators for nitrite oxidation. As a result, the Fe2O3 modified biosensor exhibited excellent performance for the determination of nitrite with a response time of <10s, linear range between 0.009 and 3mM, and sensitivity as 19.83μAmM−1. A high selectivity and long-term stability toward nitrite oxidation in the presence of glucose and l-ascorbic (AA) was also observed at their maximum physiological concentrations, which made this novel Fe2O3 nanomaterial bounded with high indexed facets promising for sensing applications in medicine, biotechnology and environmental chemistry.