The invention discloses a preparation method of a CdTe / CdS / ZnS / SiO2 quantum dot. The preparation method comprises the steps: firstly, synthesizing mononuclear CdTeQDs by using cadmium acetate, mercaptopropionic acid and sodium hydrogen telluride in a water phase; then, transferring a reaction solution of CdTeQDs which is cooled to room temperature into a precursor which contains cadmium acetate, zinc sulfate and the mercaptopropionic acid and has the pH value of 9.0-10.0, uniformly mixing and stirring, adding a sodium sulphide solution, and carrying out backflow reaction to synthesize double-shell CdTe / CdS / ZnSQDs; and finally, directly adding tetraethyl orthosilicate in a reaction solution of the CdTe / CdS / ZnSQDs, and carrying out backflow reaction to synthesize CdTe / CdS / ZnS / SiO2QDs. The preparation method is used for synthesizing the CdTe / CdS / ZnS / SiO2QDs by using a direct method and is simple to operate, needs mild conditions, and is low in cost and friendly to the environment. The synthesized product CdTe / CdS / ZnS / SiO2QDs is good in water solubility, high in stability, uniform in size and excellent in optical performance.