The invention discloses an omeprazole sodium freeze-dried powder injection and a preparation method thereof. The omeprazole sodium freeze-dried powder injection contains an active ingredient, namely, omeprazole sodium monohydrate, and auxiliary materials, namely, calcium disodium edetate and sodium hydroxide. The preparation method of the omeprazole sodium freeze-dried powder injection is characterized by comprising the following steps: weighing the calcium disodium edetate of prescription amount and dissolving the calcium disodium edetate in water for injection, stirring, dissolving, and regulating pH value to 10.0-12.0 by using 10% of sodium hydroxide solution; weighing omeprazole sodium of the prescription amount and adding the omeprazole sodium in the mixture, stirring at room temperature for dissolution, supplementing and adding the water for injection to full amount; adding active carbon, stirring at room temperature for decoloration and endotoxin removal, conducting rough filtration to remove carbon firstly, and then conducting refining filtration by using a filter membrane of 0.22 Mum; taking refining filtrate to test intermediate, conducting encapsulation after meeting requirements; and freeze-drying and unboxing, thus obtaining the omeprazole sodium freeze-dried powder injection. The freeze-drying technology of the omeprazole sodium freeze-dried powder injection takes temperature below minus 40 DEG C as pre-freezing temperature; after pre-freezing for at least two hours, sublimation is started, wherein the sublimation temperature is 5-12 DEG C, the sublimation time is over 14 hours; and then drying is conducted for over 2 hours at the temperature of 20-35 DEG C. Unboxing is carried out after a stopper is added and a cover is put in place, thus obtaining the finished product of the omeprazole sodium freeze-dried powder injection.