In our study, siRNA-mediated HMGB1 knockdown markedly reduced the PA-induced increase in the expression of HMGB1 and the release of HMGB1, TNF-α, IL-8 and IL-1β, confirming the crucial role played by HMGB1 in PA-induced NAFLD inflammation. The gene discussed is TNF; the disease is metabolic dysfunction-associated steatotic liver disease.