In this study, we found that ATF4, a critical regulator in ER stress response, is a novel target of HER2, as evidenced by: (1) expression of HER2 upregulates ATF4 expression at both mRNA and protein levels; (2) knockdown of ATF4 inhibits HER2-induced cell migration; and (3) expression of ATF4 is correlated with HER2-positive breast cancer specimens. The gene discussed is ATF4; the disease is breast cancer.