Wound healing is a complex and dynamic biological process. The efficacy and safety of a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) hydrogel to promote deep-second-degree burn wound healing is evaluated in this study. In this multicenter, randomized, double-blind, and placebo-controlled clinical trial, 90 patients with deep second-degree burns were randomly assigned into two groups. Complete healing time and percentage of wound healing at different time points were observed and side effects were recorded. A statistically significant difference was noted at each time point (p<0.01). No side effects were observed. These results suggest that rhGM-CSF hydrogel can significantly accelerate deep second-degree burn wound healing and is considered to be safe.