Members of the serum and glucocorticoid-regulated kinase (SGK) family are important mediators of growth factor and hormone signaling. To investigate the biological function of SGK family member SGK2α, eukaryotic expression plasmid pEGFP-N1-SGK2α was constructed and introduced into HEK293 cells by transient transfection. The subcellular localization of SGK2α-GFP fusion protein was preferentially localized in the cytoplasm by laser scanning confocal microscope. The interaction of SGK2α and glycogen synthase kinase 3β (GSK3β) was confirmed by coimmunoprecipitation experiment. Stable BEL7402 cell line expressing SGK2α proteins was generated by PCDNA6-V5-HisB-SGK2α plasmid transfection. The growth of BEL7402 cells was suppressed and the cell doubling time was prolonged after SGK2α gene transfection by cell proliferation experiment. Compared with the control cells, the tumorigenic capacity of BEL7402 cells was clearly decreased after SGK2α gene expression by tumorigenecity assay. Overexpression of SGK2α decreased the expression of β-catenin and Cyclin D1 but not affected the expression of GSK3β in BEL7402 cells by Western blotting. These results suggest that overexpression of exogenous SGK2α protein might inhibit tumor cell growth both in vitro and in vivo by decreasing the expression of Wnt/β-catenin signal pathway molecules.