As one of commonly used herbs with dual-purpose of drug and food, it has been reported that vitexin has hepatoprotective effects. However, the protective effects of vitexin on colitis-induced liver injury as well as the underlying molecular mechanisms remain unclear. The purpose of the current study was to investigate the effects and mechanisms of vitexin on liver injury induced by acute ulcerative colitis in mice. In this study, the mice model of acute ulcerative colitis was induced by 4 % dextran sodium sulphate (DSS). And then, the degree of liver injury in colitis mice was evaluated, the hepatic ALT, AST, TC and TG levels were measured by specific determination kits, the levels of TNF-α, IL-6 and IL-1β were examined by ELISA, the expressions of TLR4/NF-κB pathway related protein were detected by western blot analysis. The results indicated that hepatic histopathological changes induced by DSS were normalized by vitexin treatment, administration of vitexin decreased the liver levels of ALT and TC in mice with liver injury and reduced the release amounts of DSS-induced pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Furthermore, we found that vitexin inhibited the activation of TLR4/NF-κB signaling pathway induced by DSS. In conclusion, vitexin possess hepatoprotective activities against colitis-induced liver injury, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis.