Hollow carbon dots (HCDs), as drug carriers, and doxorubicin (DOX), as a model drug, were selected to prepare a HCDs–DOX-loading system. First, HCDs were prepared by a hydrothermal method and characterized by transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and nuclear magnetic resonance (¹³C NMR), UV-vis absorption, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopies (XPS). The HCDs were then used to load DOX. The drug-loading system of HCDs–DOX was characterized by zeta potential measurements, and UV-vis absorption and fluorescence spectroscopies. We then studied the drug loading, formation mechanism, cytotoxicity, in vitro release and pH-targeted properties. HCDs–DOX was found to have a high drug (DOX)-loading ratio (∼42.9%) and better sustained pH targeted-release and lower cytotoxicity than those of DOX. In the HCDs–DOX system, interactions between the HCDs and DOX were electrostatic resulting in the formation of –NC– via the coupling of –NH₂ (on HCDs) and –CO (on DOX). In vitro release of HCDs–DOX conformed to the Weibull model and Fick diffusion, consistent with that of free DOX. We report, for the first time, that the: (i) functional groups on the HCD surfaces (not their hollow structure) play a key role in drug loading; (ii) the carrier (HCDs) did not change the in vitro release model or mechanism of DOX before and after loading by the HCDs.