In our current study, we for the first time demonstrated that upon EGF induction, SHCBP1 translocates to the nucleus where SHCBP1 binds to β-catenin and augments transactivating activity of β-catenin, leading to enhanced NSCLC cellular stemness in a SHCBP1-dependent manner. Here, EGF is linked to non-small cell lung carcinoma.