The purposes of the present study were to investigate whether SIRT1-mediated HMGB1 deacetylation can modulate the release of HMGB1 during the progression of NAFLD and to explore whether SalB can protect against NAFLD via the SIRT1/HMGB1 pathway. The gene discussed is HMGB1; the disease is metabolic dysfunction-associated steatotic liver disease.