In this study, we first demonstrate that 1) TAF9 is an essential therapeutic target in the progression of NAFLD, 2) DSS can protect against HFD- and PA-induced fatty acid β-oxidation reduction and LD accumulation, and 3) DSS exerts a protective effect against NAFLD, possibly through the HDAC1/TAF9 pathway. The gene discussed is HDAC1; the disease is metabolic dysfunction-associated steatotic liver disease.