A multifunctional drug delivery system (MDDS) based on near-infrared (NIR) imaging was developed in various conformations for the accurate diagnosis and therapy of cancer. However, it remains challenging to develop an ideal structure for an MDDS with both exact and variable functionality. Herein, we report a fluorescence color-changeable branched-form heptamethine cyanine dye (PEG-4-CyP) that has both a simple structure and various functionality. The PEG-4-CyP was not only able to construct the nanoparticle (NP) structure by encapsulating DOX (PEG-4-CyP/DOX), but also showed change in the NIR fluorescence color by reacting with glutathione (GSH). The PEG-4-CyP/DOX was broken down in the redox microenvironment inside cancers because of the reduction reaction of PEG-4-CyP to GSH. As a result, the NP disruption, DOX release, and reactivity of PEG-4-CyP to GSH were visualized by NIR fluorescence color-change. Moreover, PEG-4-CyP/DOX showed an excellent chemophototherapeutic effect in cancer cells. This NIR fluorescence color-change strategy demonstrates the applicability of PEG-4-CyP as a novel MDDS able to provide a variety of information with a simple NP structure. (C) 2020 The Korean Society of Industrial and Engineering Chemistry.