Purpose To report the case of persistent corneal epithelial defect in total limbal stem cell deficiency (LSCD) after severe firework-related ocular burn treated with autologous Platelet-Rich Plasma (PRP). Case description A young patient, victim of fireworks trauma, presented with a large persistent epithelial defect affecting the central cornea of his left eye and progressing to stromal melting, in the context of grade VI ocular surface burn with 12 h limbal involvement. Impression cytology to the cornea confirmed a complete LSCD. Assessment of corneal sensitivity by Cochet Bonnet esthesiometer revealed complete corneal anesthesia. Based on progressive clinical worsening under conventional therapy, the patient was started on very pure autologous PRP eye drops obtained using the Hy-Tissue PRP® technology. Six times a day eye drops administration for 30 days was scheduled in the affected eye. At the end of treatment, the epithelial defect had disappeared being replaced by advancing conjunctiva. Conclusion Our findings provide information on management of ocular burns from fireworks, a subject of current interest and concern. Autologous PRP eye drops prepared using the Hy-Tissue PRP® system and administered in the presence of total LSCD and complete corneal anesthesia, prevented corneal stromal melting to progress and allowed the ocular surface epithelial coverage to re-establish. This paved the way for later successful restorative and reconstructive intervention. Also, first description of the Hy-tissue PRP procedure for ophthalmological use is reported.