As one of the most prospective delivery systems of insoluble drugs, nanocrystal has attracted more and more attention from pharmaceutical researchers. Nanoparticles with prominent different particle diameters were obtained to solve the problem of solubility and evaluate the positive effects of quercetin in vitro. The newly prepared nanocrystals were investigated by several methods including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The particle sizes of the quercetin nanocrystals A (quercetin/NCs-A), quercetin nanocrystals B (quercetin/NCs-B) and quercetin nanocrystals C (quercetin/NCs-C) were 3.089±0.162 μm, 677.2±9.7 nm and 169.8± 0.3 nm respectively. The crystalline state of quercetin was detected by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analyses and no change was observed after the process of reducing sizes. An accelerated quercetin dissolution rate was achieved through the nanocrystal technique. In conclusion, nanocrystals could significantly increase the equilibrium solubility of quercetin In Vitro. In addition, the particle size also had an important effect on the dissolution behavior of quercetin.