The present study aimed to investigate the role of the C‑sis gene in the apoptosis of hepatocytes in vitro and in the liver function of a rat model of fulminant hepatic failure (FHF). Buffalo rat liver (BRL) cells were treated with hydrogen peroxide (H2O2) to induce apoptosis and then transfected with a C‑sis overexpression vector. A rat model of FHF was established, and C‑sis was overexpressed. The mRNA and protein expression of C‑sis were examined using reverse transcription‑polymerase chain reaction and western blot analyses, respectively. Cell viability was assessed by CCK8, and a TUNEL assay was used to examine cell apoptosis. Flow cytometry was used for cell cycle detection. Hematoxylin and eosin staining was used for histological examination. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also examined in the rats. The results showed that C‑sis was successfully overexpressed in the cells and rat model. Compared with H2O2‑treated BRL cells, the overexpression of C‑sis significantly inhibited cell apoptosis, promoted cell viability, and decreased the expression of cleaved caspase-3. Similar results were observed in the FHF rats treated with the C‑sis overexpression plasmid, compared with those treated with empty plasmids. In addition, in the FHF rats overexpressing C‑sis, histological examination showed that liver injury was alleviated, the levels of ALT and AST were significantly decreased, and mortality rate was significantly decreased, compared with those observed in the rats treated with empty plasmids. In conclusion, the overexpression of C‑sis inhibited the H2O2‑induced apoptosis of BRL cells in vitro, and alleviated liver injury, improved liver function, and decreased mortality rates in rat models of FHF.