In this study, we conclude that the overexpression of HSP60 in HFD can ameliorate hepatocellular steatosis and liver inflammation, likely by targeting the release of mt-dsRNA and the subsequent innate immunity response, including a reduction in the TLR3/MDA5 signaling pathways, thus providing a potential target for modulating the NAFLD process. The gene discussed is HSPD1; the disease is metabolic dysfunction-associated steatotic liver disease.