The invention provides a preparation method of Esomeprazole and a preparation method of Esomeprazole sodium, and (1S,2S)-(-)-1,2- hexamethylene diamine-D-tartrate is used as a chiral ligand, cobaltous naphthenate is used as catalyst, and Esomeprazole is prepared by asymmetric oxidation of 2-(((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)sulfur-base)-1H-benzimidazole under the effect of catalyst with catalysis amount, and the prepared Esomeprazole has a better stereoselectivity and generation of peroxide sulfone is avoided. Simultaneously, sodium hypochlorite or sodium peroxide are used as oxidizing agent for preparing Esomeprazole sodium, and the sodium containing compound in the reaction process is used as oxidizing agent and sodium source, thereby the oxidation reaction and the salt forming reaction can be completed in the same reaction system with simple synthesis process.