OBJECTIVE： To establish a method for the content determination of Esomeprazole sodium for injection. METHODS： UPLC-MS/MS was performed. The column of ZORBAX Eclipse Plus C18 with 0.1％ formic acid-methanol（73 ∶ 27，V/V） at a flow rate of 0.3 ml/min， column temperature was 35 ℃， analysis time was 5 min， injection volume was 2 μl； ionization mode was positive ion mode， ion source temperature was 150 ℃， capillary voltage was 3.0 kV， cone voltage was 50 V， cone flow was 150 L/Hr， desolvation temperature was 450 ℃， desolvation gas flow was 900 L/Hr， nebuliser pressure was 7.0 Bar， parent ion scan range was 100-800 mz/mz， working mode was multiple reaction monitoring mode. RESULTS： The linear range of esomeprazole was 0.2-20.0 ng/ml（r＝0.999 7）； the limit of quantitation was 50 pg/ml； RSDs of precision， stability and reproducibility tests were lower than 2％； recovery was 99.93％-100.05％（RSD＝0.1％，n＝9）. CONCLUSIONS： The method is simple and accurate， and can be used for content determination of Esomeprazole sodium for injection.