Novel CdTe/CdS/SiO2 core/multishell fluorescent composite nanoparticles were prepared by reverse microemulsion method in this paper. Water-soluble CdTe/CdS core/shell quantum dots (QDs) were synthesized with 3-mercaptopropionic acid as the stabilizers and thiourea as the sulphur source in aqueous solution. CdTe/CdS/SiO2 fluorescent nanoparticles were obtained by hydrolysis of tetraethyl orthosilicate (TEOS) at room temperature in cyclohexane solution when polyethylene glycol tert-octylphenyl ether (Triton X-100) as the surfactant and n-hexanol as the co-surfactant. The resultant core/multishell fluorescent composite nanoparticles were inert and chemically stable in harsh environments because of the silica layer. In this paper, the diameter of these particles was about 64 nm, and the maximum emission was about 678 nm. The coating of silica could provide a great convenience for the biological functionalization of the surface of luminescent QDs and be useful to label biological molecules in vitro and vivo in the biological analyses.