In the present work, the CdSe/ZnSe core/shell quantum dots (QDs) were successfully transferred from organic phase to water phase via a two-phase solution system process by surface coating with amphiphilic polymer. Surface coating with amphiphilic polymer is an effective method, which can form stable soluble QDs in water. However, the conventional polymer coating method is performed in homogeneous phase, and it easily induces the aggregation of the QDs attributing to the long chain of enlace of the polymer. It is thus necessary and meaningful to develop surface coating technique for getting monodisperse coating QDs with amphiphilic polymer. In comparison with previously reported coating method, the authors’ experiment process is performed in two-phase solution system, and can effectively reduces the possibility of aggregation of the QDs. The resulting hydrophilic CdSe/ZnSe core/shell QDs have long term stability in water, and high quantum yield. The polymer coating process was affirmed by various characterizations. Fourier transform infrared spectra suggest that the octylamine modified polymer was successfully coated on the surface of the CdSe/ZnSe QDs. The transmission electron microscopy suggests that the size and shape of the QDs showed no obvious change before and after the coating process. Dynamic light scattering results indicate that the hydrophilic QDs exhibit narrow hydrodynamic size distribution with the mean hydrodynamic diameters of about 19.7 nm. The luminescence properties of the QDs were investigated with photoluminescence spectra and ultraviolet-visible absorption spectra. This polymer coating process has less effect on luminescence capability. The quantum yield decreased from 43% to 30%. Further, in order to confirm that the polymer capped QDs is biocompatible, the QDs were used for specific detection of the human IgG with fluorescence mapping. The specific molecular recognition capacity of goat anti-human IgG-modified QDs confirms that the polymer coated QDs have compatible functional chemical groups for bioconjugation and are suitable for biological applications.