Bright and stable CuInS2/ZnS@SiO2 nanoparticles with near-infrared (NIR) emission were competently prepared by incorporating the as prepared hydrophobic CuInS2/ZnS quantum dots (QDs) directly into lipophilic silane micelles and subsequent exterior silica shell was formed. The obtained CuInS2/ZnS@SiO2 nanoparticles homogeneously comprised remarkable both single and multi-core CuInS2/ZnS QDs, while the silica shell thickness could be controlled within 5-10 nm and their overall size was 17~25 nm. Also, the functionalized CuInS2/ZnS QDs encapsulated in the silica spheres, expedited their bioconjugation with holo-Transferrin (Tf) for further cancer cell imaging. The CuInS2/ZnS@SiO2 nanoparticles not only showed a dominant NIR band edge luminescence at 650-720 nm with quantum yield between (QY) 30%~50%, without recognized PL red shift, but also exhibited excellent photoluminescence and colloidal stability in aqueous media. Impressively, the cytotoxicity studies revealed minor suppression on cell viability under both CuInS2/ZnS@SiO2 and CuInS2/ZnS@SiO2@Tf concentration up to 1 mg/mL. The application in live-cell imaging revealed that the potential of CuInS2/ZnS QDs as biocompatible, robust, cadmium-free and brilliant NIR emitters are considered promising biological probes for fluorescent labels. KEYWORDS: CuInS2/ZnS@SiO2, Near infrared QDs (NIR), Lipophilic silane micelles, Cytotoxicity, Fluorescent labels, Cadmium-free.