The invention discloses a charged composite nanofiltration membrane based on organic-inorganic nanoparticles and a preparation method of the charged composite nanofiltration membrane. The nanofiltration membrane is composed of a supporting layer and a nanofiltration functional layer, the nanofiltration functional layer is formed by cross-linking cross-linked ionic amphiphilic polymer nanoparticles and inorganic nanoparticles, the ionic amphiphilic polymer nanoparticles are mutually cross-linked, and the inorganic nanoparticles and the ionic amphiphilic polymer nanoparticles are mutually cross-linked; the supporting layer is crosslinked with the nanofiltration functional layer through reactive groups on the surface of the supporting layer; according to the preparation method of the nanofiltration membrane, the nanofiltration membrane in a flat, hollow fiber or tubular form can be prepared, the prepared nanofiltration membrane is high in flux, efficient separation of ions and charged small molecules of different valence states can be achieved through the charge characteristic of the nanofiltration membrane, and the nanofiltration membrane is excellent in pressure resistance and has the potential of treating high-concentration brine; the method has great application value in the fields of seawater desalination, ion separation, sewage treatment, hard water softening, biological medicine, food processing and the like.