With further study by qRT‐PCR, Western blotting, and TMAs, we identified PHB2 as the preferable candidate biomarker for early metastasis of ESCC, and provided evidences for its promise roles in predicting metastasis of ESCC, as well as verified that PHB2 could play an important role in regulating the biology functions of human ESCC cell lines and promoting the occurrence and development of ESCC. This evidence concerns the gene PHB2 and esophageal squamous cell carcinoma.