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This invention relates to the field of lyophilized formulation technology and discloses a method for preparing controllable molecular weight silk fibroin lyophilized spheres, comprising the following steps: preparing a mixture of a lyophilization protectant, a protein conformation stabilizer, and silk fibroin solutions of different molecular weights. The lyophilization protectant includes sugars and sugar alcohols, and the protein conformation stabilizer is a polyol. After pre-freezing the mixture into spheres, a surface coating modification is performed by adding an ethanol solution containing cellulose, followed by a second pre-freezing in liquid nitrogen, and finally, the lyophilized product is controlled by a specific program in a vacuum freeze dryer. This invention employs specific lyophilization protectants, protein conformation stabilizers, surface coating modification techniques, and freeze-drying techniques, enabling the prepared silk fibroin lyophilized spheres to have a better appearance and improving their resistance to moisture absorption and shrinkage, as well as their rapid reconstitution.