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Objective: To investigate the anticancer effects of desacetyluvaricin (DES) on hepatocellular carcinoma (HCC) in vitro, and to study its mechanism. Materials and Methods: Using DES and cisplatin (DDP) to intervene the cell lines of hepatocarcinoma G2.2.15 (HepG2.2.15) and HepG2, by detecting the expression of HBxAg by immunofluorescence method, the cell cycle and apoptosis by flow cytometry method (FCM), and expression of NF-κB protein by ELISA. Results: DES and DDP showed to suppress proliferation of HepG2.2.15 and HepG2; they increase the S-phase cells and decrease G2/M phase cells. DES and DDP both could promote the apoptosis and reduce the expression of NF-κB on the cell line. DES and DDP both can suppress the expression of HbxAg in HepG2.2.15. There were no statistical differences of the above results between these two drugs (P > 0.05). Conclusions: DES possesses anticancer effect on hepatocarcinoma. The possible mechanism might be due to promotion the apoptosis of the cancer cells, and downregulate the expression of HBx andNF-κB protein. DES is a kind of natural products, Because of the lighter clinical side effects; our observations suggest that DES has the potential to be explored as an effective anticancer agent for HCC. [ABSTRACT FROM AUTHOR]