In this study, we investigated the biological functions of PHBP1 on ESCC tumorigenesis and the regulation mechanisms on its cognate gene PHB. Based on our results, we found that PHBP1 could activate its corresponding sense gene PHB. Mechanistically, actinomycin D assay provided evidences that PHBP1 prolonged PHB mRNA half-life. The gene discussed is PHB1P1; the disease is esophageal squamous cell carcinoma.