Herein, we report pH-responsive star-like polymers (denoted as CPO) with amphiphilic diblock copolymers poly(2-(diisopropylamino) ethylmethacrylate)-b-poly[(ethylene glycol) methyl ether methacrylate] (PDPA-b-POEGMA) grafted from β-cyclodextrin (β-CD) for efficient antitumor drug delivery. A series of amphiphilic CPO polymers were synthesized via two-step atom transfer radical polymerization (ATRP) utilizing β-CD-21Br as an initiator. Transmission electron microscopy and dynamic light scattering results demonstrated that these amphiphilic star-like polymers formed unimolecular micelles (UMs) in aqueous media and showed favorable robust micellar stability. The PDPA blocks are hydrophobic at pH = 7.4, which enabled these UMs to carry hydrophobic drugs such as doxorubicin (DOX) in their inner layer with a high drug loading content. Under an acidic environment, the hydrophobility-hydrophilicity transition of PDPA blocks induced the rapid pH-triggered release of drugs for cancer therapy. To endow these UMs with diagnostic functions, near-infrared fluorescent dye cyanine 5 (Cy5) was incorporated by post-decoration on the amine-functionalized precursor where their inner layer was replaced with copolymerized blocks of P(DPA-co-AMA). The UMs of the obtained Cy5 containing polymers (denoted as CPO-Cy5) exhibited switchable fluorescence in response to different pH conditions, where the fluorescence intensity could be enhanced by 7-fold with the change of pH from 9 to 4. The cytotoxicity experiments demonstrated that the DOX-loaded CPO or CPO-Cy5 micelles presented high cytotoxicity against HeLa and MCF-7 cancer cells but low cytotoxicity against normal L929 cells, likely implying their potential tumor-specific targeting ability. The integration of NIR imaging and effective therapeutic functions made DOX-loaded CPO-Cy5 a promising nanomedicine, providing new insights into the design of theranostic nanoplatforms.