Objective:To observe the expression of DNA dependent protein kinase catalytic subunit（DNA-PKcs) in the hepatoma tissues and mouse liver tissues of different developmental stages,so as to understand the role of DNA-PKcs in cell proliferation and tumorigenesis.Methods: Immunohistochemistry and Western blotting assay were used to observe the protein expression of DNA-PKcs in liver tissues and hepatoma tissues.The siRNA technique was used to silence the expression of DNA-PKcs in the HepG2 cells; cell proliferation assay and tumor transplantation test in nude mice were performed to evaluate the changes of the proliferation ability and tumorigenesis.Western blotting assay was also conducted to examine the expression of proliferation related proteins p-GSK3β and c-myc.Results: DNA-PKcs expression decreased in the liver tissues with the decrease of cell proliferation ability during the development of mice,and the expression level of DNA-PKcs was weak in liver tissues of adult mouse; but the DNA-PKcs protein level in the hepatoma tissues was significantly elevated (P<0.01).Cell growth curve showed that the proliferation of HepG2 cells was significantly decreased after suppression of DNA-PKcs with siRNA(P<0.01),accompanied by a suppressed tumorigenesis ability.The expression of signal pathway related protein p-GSK3β and c-myc was inhibited after DNA-PKcs silencing in HepG2 cells(P<0.01).Conclusion: DNA-PKcs expression level is closely related to the proliferation ability of liver cells.Overexpression of DNA-PKcs may participate in the development and progression of hepatoma through mediating cell proliferation via the Wnt/GSK/c-myc related signal pathway.