Introduction: Most of the primary hepatocellular carcinomas (HCC) reported worldwide are associated with chronic hepatitis or liver cirrhosis (LC). The dried flower-heads of Chrysanthemum morifolium (Compositae) are an oriental drug. They have been used as an herbal tea in Chinese folklore and have been used for the treatment of eye disease in China and Japan. In addition, this herbal medication has been found to possess anti-inflammatory, antimutagenic, and several anti-microbial activities, such as anti-bacterial, anti-fungal, anti-viral, and anti-spirochetal activities. The purpose of this study was to investigate the effect of Chrysanthemum morifolium (Cm) in CCl4-plus ethanolinduced cirrhosis and to determine the underlying mechanism. Materials & Methods: The hepato-protective effect of Cm on the animal model using CCl4-plus ethanol-induced cirrhosis was used. CCl4-plus ethanol-induced cirrhosis in rat was examined. In particular, the resulting cell damage, apoptosis, DNA damage, fibrosis, and nuclear factor-κB (NF-κB) inactivation were investigated. Results: Cm significantly suppressed fibrosis, inhibited apoptosis, and decreased the serum alanine aminotransferase (ALT) levels and binding to the NF-κB consensus sequence, which were markedly elevated in the CCl4-ethanol-treated group. Conclusion: Results suggested Cm possessed significant hepato-protective effect. Furthermore, inhibition of nuclear factor κB is associated with hepato-protective effects in CCl4-plus ethanol-induced liver fibrosis in rats. To our knowledge, this was the first study showing that Cm posses hepato-protective effect, in addition to its numerous well known traditional pharmacological effects.