The invention discloses a drug moisture-proof agent and a preparation method and application thereof,and belongs to the field of moisture-proof technologies of traditional Chinese medicine preparations. The drug moisture-proof agent comprises zein,soluble starch,calcium hydrophosphate,lactose,magnesium stearate,microcrystalline cellulose,hydroxypropyl cellulose,povidone,cane sugar,micro-powder silica gel,hydrophobic nano silicon dioxide and maltodextrin. The drug moisture-proof agent is prepared in the steps of dissolving,modifying,mixing,stirring and the like. A reinforcing system composed ofthe micro-powder silica gel,the hydrophobic nano silicon dioxide and the maltodextrin is applied to the drug moisture-proof agent,the viscosity and moisture absorption rate of the drug moisture-proofagent are further reduced,and the drug stability is improved.