Objective To observe the regulation of sry-related high-mobility-group box-containing 2 (Sox2) on epidermal growth factor receptor(EGFR)and on the sphere formation rate of glioma stem cells .Methods Promoter reporter plasmids of epidermal growth factor homologous receptor ErbB2 ,ErbB3 ,ErbB4 were respectively constructed .Sox2 expression plasmid was co-transfected together with the reporter plasmid into U251 cells .Then the luciferase activity was analyzed by dual-luciferase reporter assay sys-tem to test the regulation of Sox2 on ErbB2 ,ErbB3 ,ErbB4 promoters .Sphere formation assay was used to observe selfrenew of the cancer stem cells after transfection of Sox 2 .The expression of EGFR and ErbB2 proteins in the spheres was examined by Western blot .Results Sox2 could dose-dependently increase the ErbB2 ,ErbB3 ,ErbB4 promoter drived luciferase activity .Sox2 promotes the sphere-forming rate of U251 cells and upregulates the expression of EGFR and ErbB2 in the spheres .Conclusion Sox2 could up-regulate the expression of EGFR and promote selfrenew of glioma stem cells .