Esophageal cancer (EC) is the sixth main cause of cancer death worldwide. Important genes associated with esophageal cancer include FOXO3, AKT, and GSK3β. Excessive FOXO3 expression inhibits the proliferation of cancer cells. The expression of AKT is involved in controlling cell growth in tumors. GSK3β activity is higher in cancer tissues. Given the effective role of cancer stem cells (CSCs) in the initiation and metastasis of cancer, targeting CSCs seems to be a viable option. Various biomarkers such as CD markers are used to separate CSCs from other cells. Another way to separate CSCs is to use serum-free suspension culture. In the canonical Wnt signaling pathway, β-catenin with the E-cadherin membrane forms a complex that causes cell adhesion. Using the genes, signaling pathways, and inhibitors such as Wnt, Notch, YAP1, and Hedgehog inhibitors involved in this cancer and isolating CSCs can be considered as effective options for therapeutic purposes.