The serum- and glucocorticoid-inducible kinase SGK1 was originally cloned from mammary tumor cells. According to in vitro observations, SGK1 is upregulated by the oncogene b-catenin and negatively regulates the proapoptotic transcription factor Foxo3a, which in turn stimulates transcription of the Bcl2-interacting mediator BIM. The present study aimed to define the role of SGK1 in colon carcinoma in vivo. SGK1 knockout mice (sgk1^-/-) and their wild type littermates (sgk1^+/+) were subjected to chemical cancerogenesis (intraperitoneal injection of 1,2-dimethylhydrazine followed by three cycles of synthetic dextran sulfate sodium for 7 days). Moreover, SGK1 was silenced in HEK293 cells. Foxo3a and BIM protein abundance were determined by Western blotting and immunohistochemistry. Following chemical cancerogenesis, sgk1^-/-mice developed significantly less colonic tumors than sgk1^+/+ mice. According to Western blotting and immunohistochemistry, SGK1 deficiency enhanced the expression of Foxo3a and BIM both, in vitro and in vivo. In conclusion, SGK1 expression favors the development of colonic tumors and may be effective at least in part through downregulation of Foxo3a and BIM.