Objective: To investigate the relationship among Pokemon, NF- kappa B p65 and Bcl-2 in hepatoma cells. Methods: HCC cell HepG2, SMMC7721 and human fetal liver cell line LO2 cells were used, and expression of Pokemon, NF- kappa B p65 and Bcl-2 in three cells were detected by real-time PCR and western blot. Then siRNA of Pokemon was applied to inhibit the expression of Pokemon and NF- kappa B p65 and apoptotic rate was determined by flow cytometric analysis. Results: Expressions of Pokemon, NF- kappa B p65 and Bcl-2 in human hepatoma cell HepG2, SMMC7721 expression were significantly higher than those in human embryonic stem cells LO2. siRNA of Pokemon inhibited the expression of Pokemon, NF- kappa B p65 and Bcl-2 in liver cancer cells, and significantly increased apoptosis of liver cells. While siRNA of NF- K B p65 inhibited the expression of NF- kappa B p65 and Bcl-2, but Pokemon expression in hepatoma cells had no significant change. Conclusions: The proto-oncogene Pokemon can inhibit P14ARF by specific transcription regulation of cell cycle and can induce tumors. In addition, Pokemon can regulate NF- kappa B p65 through the expression of apoptosis repressor, and promote the development of liver cancer. It suggests signal network in the liver include the regulation of new non-classical NF- kappa B regulatory pathway.