Abstract. β-elemene is extracted from the Chinese medicinal herb Curcuma Wenyujin. It has a broad-spectrum antitumor effect on many types of cancer. However, the exact mechanism of action of β-elemene in hepatocellular carcinoma (HCC) remains unknown. Histone H1 is thought to act as a repressor of transcription by promoting the compaction of chromatin into higher order structures. We found that histone H1 plays an important role in the antitumor function of β-elemene. In this study, histone H1 expression in the H22 murine hepatocellular carcinoma cell line was confirmed, with P388D1 cells serving as a positive control. Furthermore, H22 cells were cultured with β-elemene for different time-points in vitro and treated with different dose-dependent β-elemene in an experimental H22 HCC xenograft transplantation model to confirm whether β-elemene inhibited the growth of H22 tumor cells. In addition, measurements of histone H1 expression both in vitro and in vivo enabled us to demonstrate that β-elemene affects the expression of histone H1 only at the protein level, but is not involved in regulation at the gene level. Our results clearly show that the effect of β-elemene on inhibiting the growth of H22 tumor cells is time-and dose-dependent. In conclusion, β-elemene inhibits the growth of H22 cells by enhancing the expression of histone H1 only at the protein level. This finding may provide insight into a new mechanism of the antitumor action of β-elemene.