The invention discloses a methotrexate oral sustained-release preparation and a preparation method thereof. The methotrexate oral sustained-release preparation is obtained in the mode that methotrexate is adsorbed to macroporous adsorption resin. The adopted macroporous adsorption resin comprises macroporous adsorption resin bodies ranging from non polarity to moderate polarity, the macroporous adsorption resin bodies have large specific surface areas and can adsorb methotrexate, the macroporous adsorption resin bodies adsorb methotrexate through a hydrophobic interaction or a hydrophobic interaction and hydrogen-bond interaction, the adsorbed methotrexate is slowly released in gastrointestinal tracts, and the effect of slow release is achieved. The non-polarity macroporous adsorption resin bodies are macroporous adsorption resin bodies with the poly (divinyl benzene as the framework, and the macroporous adsorption resin bodies ranging from weak polarity to moderate polarity are macroporous adsorption resin bodies with the poly (divinyl benzene as the framework and containing polar groups, such as ester groups, nitrile groups and amide group.