In this work, bismuth imbedded nanohydrogel (Bi@CMC) was synthesized with ultra-violet irradiation. A series of characterizations showed that the size of Bi@CMC was about 35–80 nm, while the imbedded bismuth particles were about 5 nm. The Bi@CMC had good stability and dispersibility, and the photothermal conversion efficiency was up to 40.21%. Methyl thiazolyl tetrazolium results showed that over 68% of the cells survived when the probe concentration reached 2 mg/mL, showing low toxicity of Bi@CMC. After the adsorption of doxorubicin, a multi-functional nanoprobe (DOX/Bi@CMC) integrating computed tomography/photoacoustic dual-mode imaging and photothermal/drug dual-mode therapy was obtained. DOX/Bi@CMC could be enriched at the tumor site through enhanced permeability and retention effect. After irradiation with near-infrared region laser, the probe could not only generate heat effect, but also thoroughly released drug through nano-hydrogel disintegration, thus achieving the purpose of chemo-photothermal combined therapy. The therapeutic effect was significantly better than that of the single mode therapy. It was also found that the probe size decreased sharply after nano-hydrogel’s disintegration, indicating that it would be metabolized more easily, and therefore, could effectively reduce the side effect and toxicity. Hematoxylin and eosin staining of main organs and blood biochemical indicators showed that the probe had good biological safety after injection. The current work proposes a new dual-mode bio-imaging and chemo-photothermal combined therapy nanoprobe, which presents good application prospects for tumor theranostic.