Hybrid SiO2-coated CdTe/CdSe quantum dots (QDs) were prepared using CdTe/CdSe QDs prepared by hydrothermal synthesis. A CdSe interlayer made CdTe/CdSe cores with unique type II heterostructures. The hybrid SiO2-coated CdTe/CdSe QDs revealed excellent photoluminescence (PL) properties compared with hybrid SiO2-coated CdTe QDs. Because of the existence of spatial separations of carriers in the type II CdTe/CdSe core/shell QDs, the hybrid QDs had a relatively extended PL lifetime and high stability in phosphate-buffered saline buffer solutions. This is ascribed to the unique components and stable surface state of hybrid SiO2-coated CdTe/CdSe QDs. During the stabilization test in phosphate-buffered saline buffer solutions, both static and dynamic quenching occurred. The quenching mechanism of the hybrid QDs was not suited with the Stern–Volmer equation. However, the relative stable surface of CdTe/CdSe QDs resulted in lower degradation and relative high PL quantum yields compared with hybrid SiO2-coated CdTe QDs. As a result, hybrid SiO2-coated CdTe/CdSe QDs can be used in bioapplications.