Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.