The present invention discloses one kind of core-shell structure quantum dot with ZnS shell, and features its chemical expression of M(1-x)Y2S4 to Ax/ZnS, where, M is Bioavailability or Ca, A is one or two of Mn, Cu, Ag, Al, Pr, Eu, Er, Tm, Ce, Yb and Nd, x is 0.001-0.5. The present invention also provides the preparation process of the quantum dot. The preparation process has safe material, low material cost, simple and safe operation and relaxed equipment requirement, and is suitable for large scale preparation in lab. The prepared quantum dot has high dispersivity, high fluorescence strength and high stability, and may be used as fluorescent labeling material for biological detection and analysis and as light emitting material for display devices.