A new targeted photothermal agent used in cancer photothermal therapy (PTT) is synthesized by co-intercalation of indocyanine green (ICG) and targeting folic acid (FA) into the interlamellar gallery of layered double hydroxide (LDH). The resulting composite material (ICG–FA/LDH) possesses an interlayer distance of 2.503 nm, and a uniform particle size with an equivalent hydrodynamic diameter of 127 nm. ICG presents a monomeric state in the LDH gallery, owing to the supermolecular interactions between the LDH host and ICG guest, which results in a largely-enhanced photothermal conversion efficiency. In vitro tests performed with KB cells demonstrate a highly enhanced cellar uptake and excellent imaging ability for the ICG–FA/LDH. The photothermal conversion studies show that an ultra-low dosage of ICG–FA/LDH (equivalent ICG 10 μg mL⁻¹) under weak near-infrared (NIR) irradiation (8 min; 1.1 W cm⁻²) achieves a significant temperature increase from 19.8 °C to 51.0 °C. Therefore, a satisfactory in vitro PTT effectiveness of the ICG–FA/LDH composite is obtained, and it exhibits cellular damage as high as 87.4% with an ultra-low dosage of ICG (8 μg mL⁻¹) and weak NIR irradiation (1.1 W cm⁻², 12 min). In addition, the photothermal agent ICG–FA/LDH displays good targeting capability, biocompatibility and low cytotoxicity. It is expected that the unique ICG–FA/LDH with integrated fluorescence imaging and photothermal therapy can be potentially used in the cell labeling and PTT area.