The invention discloses a nanofiltration membrane with a nanometer hybridized desalination layer. The desalination layer formed through interphase hybridization of an inorganic nanoparticle with a particle size of 1 to 1000 nm and polyamide or polyimide is arranged on a porous supporting layer of the membrane. A preparation method for the nanofiltration membrane mainly comprises the following steps: pre-dispersion of the nanoparticle, preparation of a solution A, preparation of a solution B, interfacial polymerization, surface polishing and roller squeezing, rinsing with deionized water, moisture retention with glycerin and drying, wherein air drying and sulfonation can be carried out after surface polishing and roller squeezing. According to the invention, nanometer hybridization effects of a high polymer nano-material in the nanofiltration membrane are made full use of, so hydrophilic performance, antioxidation performance and anti-pollution performance of the nanofiltration membrane are improved, and the nanofiltration membrane has the advantages of low pollution, great flux and a high removal rate. The preparation method is scientific and reasonable, enables the nanometer composite nanofiltration membrane with a specific nanoparticle and polyamide hybridized desalination layer to be prepared and has higher ion selectivity, low pollution capability and temperature stability.