The invention discloses a preparation process of amoxicillin sodium crystal, which specifically comprises the following steps of: adding distilled water and amoxicillin in proportion to 3-neck flask in turn, heating in water bath, stirring, adding sodium salt powder slowly in proportion until the solution is clear after the suspension is formed fully, then extracting to remove the solid impurities, putting the filtrate in a crystallizer, adding entrainer in proportion, conducting vacuum azeotropic distillation, adding entrainer again in proportion after a certain amount of entrainer is distilled, conducting temperature-controlled cooling crystallization after a certain amount of water is distilled, then filtering and drying to obtain an amoxicillin sodium crystal product. The amoxicillin sodium crystal obtained by the preparation process provided by the invention has the advantages of uniform particle size distribution, high purity, good fluidity, good stability, low production cost, easiness of operation and small environmental pollution.