Objective To explore the effect of early escharectomy and large-scale autografting on serological indexes in patients after wound healing of hand deep second-degree burn. Methods A total of 80 patients with hand deep seconddegree burn admitted to our hospital from January to December 2023 were selected as the research subjects. According to the random number table method, they were divided into the control group (n =40) and the observation group (n =40). The control group received conventional treatment, and the observation group received early escharectomy and large-scale autografting. The treatment effect, serological indexes, complications and treatment satisfaction were compared between the two groups. Results The total effective rate of treatment in the observation group was 95.00%, which was better than 60.00% in the control group (P <0.05). After treatment, the levels of IL-10, ICAM-1 and EGF in the observation group were all better than those in the control group (P <0.05). The incidence of complications in the observation group was 2.50%, which was lower than 30.00% in the control group (P <0.05). The treatment satisfaction rate in the observation group was 95.00%, which was higher than 62.50% in the control group (P <0.05). Conclusion The application of early escharectomy and large-scale autografting for patients after wound healing of hand deep second-degree burn has a good effect. It can effectively improve the serological indexes of patients, reduce the incidence of complications, and increase the treatment satisfaction, which is worthy of clinical application.