Sepsis is a severe systemic inflammatory response syndrome caused by bacterial, fungal, viral, or parasitic infections. During sepsis, proinflammatory cytokines play a key role in initiating the inflammatory process. It is still urgently needed to develop novel drugs for sepsis treatment. Dihydroresveratrol is a polyphenol derivative belonging to phenylpropane, which has anti-inflammatory, antifibrosis, antiaging, and antitumor effects, whereas the role of dihydroresveratrol in sepsis is still unclear. In this study, we observed that dihydroresveratrol improved septic liver injury. We further observed that dihydroresveratrol decreased the expression of inflammatory cytokines and oxidative damage to rat liver tissues. Dihydroresveratrol improved liver injury in septic rats via regulating nuclear factor-kappa B signaling pathway.