The invention discloses AgInSe2 nanocrystalline and a preparation method thereof. The preparation method comprises the following steps: mixing and uniformly stirring silver nitrate, indium chloride and/or indium chloride tetrahydrate, selenium dioxide, polyvinylpyrrolidone and dimethyl formamide to obtain a precursor liquid; allowing the precursor liquid to have a constant-temperature reaction in a high-pressure kettle at the temperature of 160-220 DEG C for 3-20 hours to obtain the AgInSe2 nanocrystalline, wherein the AgInSe2 nanocrystalline is a metastable orthorhombic crystal system of which the space group is Pna21 and is soluble in water. The preparation method disclosed by the invention adopts simple and cheap raw materials and is simple in process, short in synthesis period, good in repeatability and environment-friendly; and the prepared AgInSe2 nanocrystalline can be well dispersed in a water phase and has application advantages in the fields such as biomedicines and water-phase optical catalysis.