Considering the potential mechanism of the SLC39A6 in ESCC, we performed in vitro functional analyses in the current study and showed that the suppression of the SLC39A6 expression modulated the malignant phenotype of ESCC cells, abrogated cell invasion, and induced an EMT phenotype in ESCC cell lines. The gene discussed is SLC39A6; the disease is esophageal squamous cell carcinoma.