Random flaps are primarily employed in clinical practice for wound repair; however, the ischemic necrosis following surgery remains a significant challenge. To address this issue, we developed high-performance near-infrared (NIR) photothermal agent, 6BQ, to enhance random flaps survival through mild photothermal therapy (MPTT). In this study, we assessed the effects of 6BQ NPs on cell viability, proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) using MPTT in vitro. Techniques such as Cell Counting Kit-8(CCK8), wound scratch assay, Transwell assay, tube formation assay, RT-qPCR, and Western blotting were employed, along with an exploration of the related signaling mechanisms. In animal experiments, we utilized the McFarlane flap model in Sprague-Dawley rats, randomly assigning them to Control, 6BQ NPs, and 6BQ NPs + laser irradiation (6BQ NPs + L) groups. On postoperative day 7, we evaluated flap viability, assessed microcirculatory perfusion with laser Doppler flow imaging, and examined angiogenesis, inflammatory response, oxidative stress, and the activity of the Heat shock protein 90(HSP90)/ Hypoxia-inducible factor 1 alpha (HIF-1α) axis using immunological and molecular biological techniques. Results indicated that under 808 nm laser irradiation (0.5 W/cm, 15 min), 6BQ NPs activated the HSP90/HIF-1α axis through MPTT, promoting angiogenesis by upregulating Vascular endothelial growth factor (VEGF) expression. Concurrently, Superoxide dismutase (SOD) content increased while Malondialdehyde (MDA) content decreased through upregulation of Heme oxygenase-1(HO-1) expression, alleviating oxidative stress, and reduced Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) expression inhibited the inflammatory response, thereby significantly improving random flaps survival. In conclusion, this study highlights the potential of 6BQ NPs in improving random flaps survival, offering a novel therapeutic strategy for wound repair.