Heretofore, conjugated polymers (CPs) attract considerable attention in photothermal therapy (PTT). Although various CPs with different structures have been reported, the suboptimal circulation persistence and biodistribution limit their efficacy in tumor treatment. Human serum albumin (HSA), an endogenous plasm protein, has been widely functioned as a carrier for therapeutic agents. Herein, we construct nanocomplexs C16 pBDP@HSA NPs from hydrophobic 4, 4-difluoro-4-bora-3a, 4adiaza-s-indacene (BODIPY)-containing CPs and HSA, which exhibit robust stability in physiological conditions and excellent photothermal activity upon irradiation. The high photothermal conversion efficiency of 37.5 %, higher than that of other reported PTT agents such as gold nanorods, phosphorus quantum dots and 2D materials, results in the potent photocytotoxicity towards cancer cells. Simultaneously, C16 pBDP@HSA NPs’ capabilities of near infrared fluorescence and photoacoustic imaging can provide guidance to the PTT. The outstanding inhibition of tumor growth results from great photothermal activity, the benefited accumulation in tumor and optimal timing of treatment. To the best of our knowledge, this is the first study which combines the BODIPY-based CPs and HSA in one nanostructure and finds application in cancer treatment. Moreover, this article also offers a new strategy for other insoluble macromolecules to explore more biomedical applications.