Cadmium sulfide semi-conductor nanocrystalline wet-soild phase reaction preparation method comprises the following steps : mixing thioglycolic acid with cadmium chloride according to mol raito 1.8-2.2:1, grinding, adding deionized water to scouring off excess thioglycollic acid, filtering, rinsing filter cake with deionized water, mixing filter cake and sodium sulfide according to 1-3.5:2 mol ratio, grinding, obtaining light yellow solid, dissolving the above-mentioned light yellow solid in water, adding into acetone or ether, depositing the CdS sol, filtering, rinsing, drying, obtaining nano CdS crystal. Reaction condition of the inventive is temperate, inventive process is simple, yield is high, grain size of prepared granule is uniform, not congregate. The invention has good repeatability. compared with traditional bioluminescence probe(organic dye), excitation spectrum of nano crystal is broad, and continuously distributed, while emission spectrum is symmetrically distributed and narrow, color is adjustable, which has a good application prospect in bioluminescence probe.