Objectives To investigate the effect of retinoblastoma-binding protein 2 (RBP2) on epithelial-mesenchymal transition (EMT) in esophageal squamous cancer cells and to compare the effect of RBP2 in lung squamous cancer cells and esophageal squamous cancer cells. Results When transfected with RBP2 siRNA, the migrated cells were 36.3 +/- A 6.03 by transwell migration assay, compared to 107 +/- A 6.7 cells in the control group. The mRNA level of epithelial cadherin (E-cadherin) was 1.54 +/- A 0.14 times higher than in the control group, and that of neural cadherin (N-cadherin) fell to 0.76 +/- A 0.03 times. The relative luciferase activity of E-cadherin promoter rose to 3.84 +/- A 0.23 times. Correspondingly, the expression of E-cadherin protein increased and that of N-cadherin protein decreased. When SK-MES-1 cells were transfected with RBP2 siRNA, their relative mRNA level of E-cadherin was 8.6 +/- A 0.37 times as high as that in control group, which was higher than that in Eca-109 cells. The E-cadherin protein was also greater in SK-MES-1 cells. Conclusion RBP2 could induce EMT in esophageal cancer cells and exert a greater effect on the expression of E-cadherin in lung squamous cells than in esophageal squamous cells.