Objective To investigate whether shikonin (SHI) can promote burn wound healing in rats by regulating the Hippo-Yes-associated protein（YAP）signaling pathway. Methods Burn models were established in SD rats and randomly assigned into groups: the model (Mod) group, L-SHI group, H-SHI group (with SHI applied to the burn wound at doses of 4 mg/cm2 or 8 mg/cm2), and the H-SHI + verteporfin group (with 8 mg/cm2 SHI applied to the burn wound followed by intraperitoneal injection of 100 mg/kg verteporfin, an inhibitor of the Hippo-YAP signaling pathway), with 10 rats in each group. Another 10 rats were included as the control (Ctrl) group, and both the Ctrl and Mod groups received an equivalent volume of saline externally. Wound healing rates were calculated on days 3, 7, and 14. HE staining was performed to evaluate epidermal repair and tissue structure. Immunohistochemistry was used to detect CD31-positive cells. Serum levels of interleukin(IL)-6, tumor necrosis factor α(TNF-α), and IL-1β were measured by ELISA. Western blotting was conducted to detect the protein expression levels of macrophage stimulating 1(MST1), p-MST1, large tumor suppressor kinase 1(LATS1), p-LATS1, YAP, p-YAP, connective tissue growth factor(CTGF), cysteine-rich angiogenic inducer 61(CYR61), and vascular endothelial growth factor(VEGF). Real-time PCR was performed to detect the expression changes of related genes. Results Compared with the Ctrl group, the Mod group showed reduced epidermal thickness, degeneration and necrosis of dermal fibrous tissue, aggravated inflammatory infiltration, more scab residue on the wound, elevated serum levels of IL-6, IL-1β, and TNF-α, and decreased CD31-positive rate, protein levels of p-MST1/MST1, p-LATS1/LATS1, p-YAP/YAP, CTGF, CYR61, and VEGF, as well as mRNA levels of MST1, LATS1, YAP, CTGF, CYR61, and VEGF (P<0.05). Compared with the Mod group, the L-SHI and H-SHI groups exhibited new epidermal layer formation, connective tissue and angiogenesis, complete scab shedding, reduced levels of IL-6, IL-1β, and TNF-α, and increased wound healing rate, CD31-positive rate, protein levels of p-MST1/MST1, p-LATS1/LATS1, p-YAP/YAP, CTGF, CYR61, and VEGF, as well as mRNA levels of MST1, LATS1, YAP, CTGF, CYR61, and VEGF (P<0.05). Compared with the H-SHI group, the H-SHI+Verteporfin group showed abnormal epidermal structure, increased inflammatory infiltration, incomplete scab shedding, elevated serum levels of IL-6, IL-1β, and TNF-α, and decreased wound healing rate, CD31-positive rate, protein levels of p-MST1/MST1, p-LATS1/LATS1, p-YAP/YAP, CTGF, CYR61, and VEGF, as well as mRNA levels of MST1, LATS1, YAP, CTGF, CYR61, and VEGF (P < 0.05). Conclusion SHI has the potential to promote angiogenesis and reduce inflammatory responses by activating the Hippo-YAP signaling pathway, thus accelerating wound healing in burned rats.