Experiments showed that PHB2 could significantly promote the proliferation and cell invasive ability of human ESCC cell lines and the knockdown of PHB2 suppressed the phosphorylation level of AKT, MMP9, and RAC1, which also involved in the metastasis mechanisms of some cancer cells, which indicated that PHB2 may be associated with the postoperative metastasis of ESCC via AKT signal. This evidence concerns the gene PHB2 and esophageal squamous cell carcinoma.