Herpetospermum caudigerum (H. caudigerum; HC), popularly known as Sejimeiduo in Tibet, it is widely used in Tibetan traditional medicine for the treatment of dyspepsia, liver and colic diseases. This study was designed to evaluate the effect of H. caudigerum extract (HCE) on suppressing liver injury induced by carbon tetra chloride (CCl4). For this purpose, we used CCl4 to induce acute liver injury in mouse model. The protective effects of HCE against liver injury were evaluated by biochemical parameters, histopathological and immunohistochemical staining. The results showed that the superoxide dismutase (SOD) activity was significantly increased with the increasing dose of HCE as compared to the CCl4-treated group (p less than 0.01); while AST and ALT levels in serum, MDA and MPO in liver were reduced in a dose-dependent manner. The histopathology showed that HCE treatment promoted the recovery of histopathological changes in liver in a dose-dependent way. Meanwhile, there was a higher expression of caspase-3 and NF-κB in the nucleus of several liver cells in the CCl4-induced group, and a low expression of caspase-3 and NF-κB were found with the increasing dose of HCE. Therefore, the present study suggests that HCE is a potent hepatoprotective agent that can treat acute liver injury and this ability may be attributed towards its anti-inflammatory and antioxidant potential.