Treatment of liver fibrosis and cirrhosis remains a challenging field. Hepatocyte injury and the activation of hepatic stellate cells are the 2 major events in the development of liver fibrosis and cirrhosis. It is known that several Chinese herbs have significant beneficial effects on the liver; therefore, the purpose of the present study was to investigate the therapeutic effect of saikosaponin-d (SSd) on liver fibrosis and cirrhosis. A rat model of liver fibrosis was established using the dimethylnitrosamine method. Liver tissue and serum were used to examine the effect of SSd on liver fibrosis. A hepatocyte culture was also used to investigate how SSd can protect hepatocytes from oxidative injury induced by carbon tetrachloride. The results showed that SSd significantly reduced collagen I deposition in the liver and alanine aminotransferase level in the serum. Moreover, SSd decreased the content of TGF-beta1 in the liver, which was significantly elevated after dimethylnitrosamine induced liver fibrosis. Furthermore, SSd was able to alleviate hepatocyte injury from oxidative stress. In conclusion, SSd could postpone the development of liver fibrosis by attenuating hepatocyte injury.