In summary, we identified and further investigated PHB2 might be considered as a potentially prognostic marker for predicting the early R/M of ESCC after radical resection and could promote proliferation and metastasis of human ESCC cells through activating AKT signaling pathway, which provides a theoretical basis for further mechanism research on ESCC R/M. This evidence concerns the gene PHB2 and esophageal squamous cell carcinoma.