Hepatocarcinogenesis is a prerequisite to hepatocellular carcinoma (HCC), which is one of the most common cancers among humans. Therefore, it is important to search for agents that protect against hepatocarcinogenesis. The present study aimed to investigate the protective effects of a combination of taurine and curcumin against experimental hepatocarcinogenesis induced by diethyl nitrosamine (DENA) in a rat model. A total of 100 rats were divided into eight groups. Eight weeks following DENA injection and treatment with curcumin and taurine, the rats were sacrificed to obtain blood and hepatic tissue samples for the evaluation of various markers and histopathological observations. Serum levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), α-fetoprotein (AFP) and α-L-fucosidase (AFU) were determined. Rats injected with DENA for eight weeks showed a high percentage of malignant changes in hepatic tissues, as well as a significant increases in the serum levels of AFP and AFU and significant reductions in the serum levels of IL-2 and IFN-γ. Treatment with curcumin and taurine markedly reduced the extent of malignant changes in the rat liver tissues, with their liver tissues showing patterns similar to that of the normal control rats. In addition, this combination resulted in normal serum levels of IL-2, IFN-γ, AFP and AFU. The results of the present study suggested that a combination of curcumin and taurine may be a novel prophylactic agent against hepatocarcinogenesis in high-risk groups exposed to chemical hepatocarcinogens.