Cancer is undoubtedly a major threat to human health because of its complexity and versatility over the past few years. Photothermal therapy (PTT) under near-infrared (NIR) light can cause thermal ablation to kill cancer cells. However, NIR-triggered PTT at temperatures > 50 °C induces inflammatory disease in nearby organs, leading to off-target effects. The inability to reach active temperatures within the tumor also limits therapeutic efficacy. Tumor killing at low temperatures is therefore critical to the effectiveness of PTT in the clinic. In this study, ultrathin boron nanosheets (B-NSs) were synthesized through simultaneous thermal oxidation etching and liquid exfoliation to control the thickness of the B-NSs at nanoscale levels. Gambogic acid (GA), a natural Hsp90 inhibitor that enhances heat-induced damage was loaded onto the PEGylated B-NSs (B-NSs-PEG/GA). The B-NSs-PEG/GA under a mild NIR-triggered heating was able to induce apoptosis in tumor cells at low temperature (~43 °C). In summary, this highlights the unique low-temperature PTT strategy to effectively kill cancer cells through minimally invasive procedures. This work was financially supported by the Guangdong Provincial Natural Science Foundation of China (2018A030310623) and the Guangdong Provincial Medical Scientific Research Foundation of China (A2019027).