The present disclosure belongs to a field of biomedical imaging technology, and in particularly to a non-uniform excitation field-based method and system for performing a magnetic nanoparticle imaging. The present disclosure includes: separating the non-uniform excitation field into independent space and current time functions by a spatialtemporal separation method; calculating a normalized signal peak through the current time function; constructing a reconstruction mathematical model based on the normalized signal peak and an imaging subunit volume; and quantitatively reconstructing a spatial distribution of a nanoparticle by combining the normalized signal peak, a non-uniform spatial function of the excitation field and the reconstruction mathematical model, so as to achieve the magnetic nanoparticle imaging of a to-be-reconstructed object.