To investigate the effect of VSD combined with epidermal growth factor on wound healing and inflammatory stress response in deep burn. Methods A total of 62 patients with deep burn admitted to our hospital from November 2022 to November 2023 were randomly divided into control group and observation group, with 31 patients in each group. The control group was treated with VSD technology and saline irrigation, and the observation group was treated with epidermal growth factor on the basis of the control group. The wound healing and inflammatory stress response were compared between the two groups. Results The wound healing time of the observation group was shorter than that of the control group, and the number of scar formation and infection was lower than that of the control group (P <0.05). The levels of IL-1, TNF-α, E, NE and R in the observation group were lower than those in the control group (P <0.05). Conclusion VSD combined with epidermal growth factor can promote wound healing in patients with deep burn, improve wound healing and reduce inflammatory stress response.