Objective? To explore the effect of recombinant human epidermal growth factor (rhEGF) gel, negative pressure sealing drainage combined with escharectomy and skin grafting on patients with deep burn and the influence on the levels of inflammatory factors, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), so as to provide basis for clinical treatment of the disease. Methods 70 cases of patients with deep burn admitted to Zhangjiagang Aoyang Hospital from February 2020 to December 2021 were selected and divided into two groups according to the random number table method, 35 cases in each group. The patients in the control group were treated with escharectomy and skin grafting, on this basis, patients in the observation group were treated with rhEGF gel and negative pressure sealing drainage. All patients were treated continuously for 7 days. The clinical indexes, serum levels of inflammatory factors, VEGF, MMP-9 and TIMP-1 before and 7 days after operation, and the incidence of complications were compared between the two groups. Results? The wound recovery time of the observation group was significantly shorter than that of the control group, and the survival rate of skin graft was significantly higher than that of the control group; compared with before operation, the level of white blood cell count (WBC), and serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), C-reactive protein (CRP) and MMP-9 in the two groups all decreased significantly 7 days after, and the observation group was significantly lower than the control group; the levels of VEGF and TIMP-1 in the observation group were significantly higher than those in the control group; the incidence of infection, fluid accumulation, elastic blisters and bleeding in the observation group were significantly lower than those in the control group (allP<0.05). Conclusion rhEGF gel, negative pressure sealing drainage combined with escharectomy and skin grafting for patients with deep burn can improve the treatment effect, reduce the inflammatory reaction of the body, be conducive to angiogenesis, and promote wound healing, and which has high security.