Both inflammation and fibrosis are essential in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Taking inflammatory cytokines and signaling pathways as vital mediators, the inhibition of inflammation response may be an effective approach for treating NAFLD. a19, a resveratrol-curcumin hybrid, has been confirmed to exhibit a good anti-inflammatory activity by preventing LPS-induced inflammatory response in macrophages. The study aims to evaluate the protective effect of a19 on high fat diet (HFD)-induced NAFLD. In the present study, compound a19 significantly inhibited the HFD-induced lipid accumulation, liver injury, liver inflammation and fibrosis in mouse model. In vitro, a19 obviously suppressed the expression of PA-induced inflammatory cytokines and fibrosis markers mRNA. Meanwhile, the anti-inflammatory effect of a19 was found to be associated with the inhibition of ERK signal pathway. These results indicated that a19 can be potentially used as a protective agent for NAFLD.