The invention belongs to the field of pharmaceutical preparation and particularly relates to a preparation method of sodium 5-ethyl-5-(1-methylbutyl)barbiturate used before calming, hypnosis and anesthetization and as an anticonvulsant drug. The preparation method utilizes a 5-ethyl-5-(1-methylbutyl)malonylurea compound as a raw material. The preparation method comprises that A, 5-ethyl-5-(1-methylbutyl)malonylurea in an acetone solution and a methanol solution of sodium methylate undergo a reaction to produce a wet product of sodium 5-ethyl-5-(1-methylbutyl)barbiturate, and B, the product is subjected to vacuum drying to form a sodium 5-ethyl-5-(1-methylbutyl)barbiturate finished product. The preparation method has the advantages of stable processes, simple operation, short production period, good product quality, high purity, high yield, low production cost, low energy consumption, recovery and recycling of a mother liquid, few three wastes and industrial production feasibility.