The invention provides a preparation method of ceftriaxone sodium. The preparation method includes steps of (1) cooling dichloromethane, methyl alcohol and water mixed solvent, adding 7-ACT and AE (active ester) and trimethylamine, controlling the temperature and timing to react; (2) sequentially adding sodium hydrogen sulfite, sodium acetate and sodium hydroxide and stirring; adding extractant, stirring, standing and splitting phase; extracting extractant by water and splitting phase, and combining water phase; (3) adding extractant under water-phase stirring, transferring to and filling in a pressure container, removing air bubbles and vibrating hermetically, and taking out after freezing with temperature controlled; (4) removing organic phase, adding activated carbon after solids are melted, stirring to decolorize, and filtering in a decarbonized and aseptic manner; adding filtrate into solvent to crystalize, filtering, washing, drying and packaging. The preparation method is low in technique cost, moderate and safe in reaction conditions, convenient to operate and facilitates industrial production, and the obtained product conforms to quality requirements and has the advantages of few impurities and good crystal forms.