A tacrolimus slow-release mini-pill and a preparation method thereof are disclosed, the tacrolimus slow-release mini-pill includes a drug-containing mini-pill and a coating layer, the drug-containing mini-pill is coated with the coating layer, the drug-containing mini-pill comprises 5mg of tacrolimus, 70mg of a blank pill core, 120-220mg of a filler, 25-125mg of a lubricant and 5-50mg of a binder, the coating layer comprises 35-175mg of Eudragit NE30D and 5-52mg of talc powder, preparation steps of the preparation method are as follows: 1, preparing materials; 2, mixing; 3, preparing the binder; 4, pelleting; 5, preparing a coating agent; 6, coating; 7, filling; and 8, aluminum molding and finishing. The tacrolimus slow-release mini-pill is used for preventing of graft rejection reaction after liver or kidney transplantation and treatment of graft rejection reaction which cannot be controlled by other immunosuppressive drugs after liver or kidney transplantation, and the tacrolimus slow-release mini-pill is more secure, better in stability, and smaller in adverse reactions.