Photothermal therapy (PTT) has attracted great attention as an anticancer treatment strategy. With the rapid development of nanomedicine, multifunctional inorganic nanophotothermal agents provide a new way to improve the effect of PTT. Herein, bovine serum albumin (BSA)-modified Bi nanosheets (Bi NSs) with good biocompatibility were synthesized by a facile redox and ball milling method and applied as a photothermal agent for the enhancement of PTT. Owing to the strong near-infrared absorption, Bi NSs exhibit high photothermal conversion efficiency (η = 36.17%) under 808 nm laser irradiation and can serve as a nanotherapeutic agent for cancer therapy. In addition, in vitro cell safety analysis also suggests that the toxicity of BSA-modified Bi NSs is negligible. Upon 808 nm irradiation, the uptake ability of tumor cells to Bi NSs@BSA has been improved. Moreover, Bi NSs@BSA also can be used as a good contrast agent for CT imaging and then to observe the distribution of materials in the tumor site. Finally, Bi NSs@BSA-mediated PTT results show a high ablation rate of A549 tumor cells both in vitro and in vivo. All results reveal that Bi NSs@BSA is a promising nanotherapeutic platform for PTT.