ObjectiveThe aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. MethodsForty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. ResultsCompared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). ConclusionModified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.