In vitro, we demonstrated that YWHAE acts as a tumor suppressor in GC inducing cell arrest and inhibiting cell invasion and migration through the down-regulation of MYC and CDC25B. On the other hand, MYC oncogene is able to induces GC cell proliferation, invasion and migration through the up-regulation of CDC25B and down-regulation of YWHAE. Our findings suggest that YWHAE and MYC may have a opposite role in GC cells. Here, YWHAE is linked to gastric cancer.