Background: Esophageal cancer is one of the most common gastrointestinal tract cancers. In cancer cells, interactions take place between apoptosis and cell proliferation and there is a positive correlation between BAX and BCL-2 genes expression levels and cancerous process. The MICAL-2 gene encodes monooxygenase enzyme which causes F-actin instability. Increasing the expression of this gene plays an important role in Epithelial-mesenchymal transition in cancerous tissue and consequently causes metastases. Since no study of MICAL-2, BAX, and BCL2 genes in esophageal cancer has been reported, the present study aimed to determine the expression of these genes in esophageal cancer patients in Kerman, Iran, in 2017-2018 using Real Time RT-qPCR. Materials and Methods: A case-control study was designed to determine the changes in the expression level of BAX, BCL2, and MICAL-2 genes. A total of 40 samples (20 fresh tissues and 20 Paraffin Embedded tissues) and marginal non-tumor control tissues were obtained. First, total mRNAs of the samples were extracted, and then after cDNA synthesis, the expression rates of MICAL2, BAX, and BCL2 were determined using Real-Time RT-qPCR. The data were analyzed using descriptive and deductive statistic methods (Generalized Linear Models) at α < 0. 05 via SPSS software (v. 20). Results: The expression levels of MICAL2 (1. 2%) and BCL2 (2. 04%) in patients with esophageal cancer were higher than those of normal tissues, while BAX (0. 46%) gene expression in the normal tissue was higher than that of the cancerous ones. In the pathologic study, it was found that 62. 5% of the samples were esophageal squamous cell carcinoma. Conclusion: Regarding the changes in the expression of BAX, BCL2, and MICAL2 genes in esophageal cancer, for determination of the expression level in individuals who have a family history of this problem, these genes can be used as biomarkers, because the diagnosis of cancer in the early stages have definitely a better response to therapies.