Esophageal cancer is a common digestive tract cancer, which is a serious threat to humanhealth. Ribophorin II (RPN2) is a part of an N-oligosaccharyltransferase complex, which isexcessively expressed in many kinds of cancers. In the present study, we explore the biological role of RNP2 in esophageal cancer. First, we found that the expression of RPN2 washigher in esophageal cancer tissues than in adjacent non-tumor tissues, and negatively correlated with E-cadherin expression. RPN2 expression levels in esophageal cancer tissueswere positively associated with differentiation and tumor node metastasis (TNM) stage. Furthermore, the expression of RPN2 was increased significantly in esophageal cancer celllines compared with normal cells. The effect of RPN2 down-regulation on cell proliferation,cell migration, and cell invasion was examined by cell counting kit-8 (CCK8), wound healingassay, and Transwell assay, respectively. Silencing RPN2 effectively inhibited cell proliferation of esophageal cancer cells in vitro and in vivo. Cell migration and invasion were alsoweakened dramatically by siRPN2 treatment of esophageal cancer cells. In addition, proteinexpression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP-2),and E-cadherin in esophageal cancer cells was determined by Western blot analysis. PCNA,MMP-2, E-cadherin, Snail and phosphorylation-Smad2/3 expression was also regulated notably by siRPN2 treatment. These findings indicate that RPN2 exhibits oncogenetic capabilities in esophageal cancer, which could provide novel insights into esophageal cancerprevention and treatment.Esophageal cancer is a common digestive tract cancer, which is a serious threat to humanhealth. Ribophorin II (RPN2) is a part of an N-oligosaccharyltransferase complex, which isexcessively expressed in many kinds of cancers. In the present study, we explore the biological role of RNP2 in esophageal cancer. First, we found that the expression of RPN2 washigher in esophageal cancer tissues than in adjacent non-tumor tissues, and negatively correlated with E-cadherin expression. RPN2 expression levels in esophageal cancer tissueswere positively associated with differentiation and tumor node metastasis (TNM) stage. Furthermore, the expression of RPN2 was increased significantly in esophageal cancer celllines compared with normal cells. The effect of RPN2 down-regulation on cell proliferation,cell migration, and cell invasion was examined by cell counting kit-8 (CCK8), wound healingassay, and Transwell assay, respectively. Silencing RPN2 effectively inhibited cell proliferation of esophageal cancer cells in vitro and in vivo. Cell migration and invasion were alsoweakened dramatically by siRPN2 treatment of esophageal cancer cells. In addition, proteinexpression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP-2),and E-cadherin in esophageal cancer cells was determined by Western blot analysis. PCNA,MMP-2, E-cadherin, Snail and phosphorylation-Smad2/3 expression was also regulated notably by siRPN2 treatment. These findings indicate that RPN2 exhibits oncogenetic capabilities in esophageal cancer, which could provide novel insights into esophageal cancerprevention and treatment.