Objective To investigate the effect of calcium voltage gated channel subunit α 1C antisense RNA2 (CACNA1C-AS2) on malignant biological characteristics of esophageal cancer cells by regulating epithelial mesenchymal transition (EMT). Methods CACNA1C-AS2 expression levels in paracancerous tissues and esophageal cancer tissues were analyzed by TCGA database. Real-time quantitative PCR was used to detect the expression of CACNA1C-AS2 mRNA in esophageal cancer cells. Following the knockdown and high expression of CACNA1C-AS2 in esophageal cancer cells, the viability of the cells was tested by MTT assay and cell colony formation assay. TranswellTM chamber method was used to measure the invasion and longitudinal migration of the cells. The horizontal migration ability of the cells was evaluated by wound healing test. The apoptosis rates of cells were detected by flow cytometry. Western blot analysis was used to detect the expressions of N-cadherin, vimentin and slug. Results CACNA1C-AS2 expression levels were low in esophageal cancer tissues and cell lines. After knocking down the expression of CACNA1C-AS2 in EC-9706 cells and Eca-109 cells, the ability of invasion and migration and viability of esophageal cancer cells were significantly enhanced, and the apoptosis rates were decreased, while the expressions of N-cadherin, vimentin and slug were up-regulated. However, the results are opposite via the over-expression of CACNA1C-AS2. Conclusion CACNA1C-AS2 enhances the proliferation, invasion and migration of esophageal cancer cells by promoting EMT.