Esophageal cancer (EC) is the eleventh most commonly diagnosed cancer, and its prognosis remains poor. Several challenges remain for improving the clinical outcomes of EC, and improving technologies for early detection, diversifying treatment options, and advancing personalized treatment are essential. Alterations in the intestinal and esophageal microbiota are associated with the pathogenesis and progression of EC; for instance, is important in the pathogenesis and progression of esophageal squamous cell carcinoma. Therefore, a novel diagnostic biomarker may be identified using the intestinal microbiota. Furthermore, targeting the intestinal and esophageal microbiota may help in the early detection of EC, use of a novel prognostic biomarker, and even the detection of a therapeutic target, resulting in a more individualized therapeutic approach for EC. In this review, we summarize the clinical research focused on the intestinal and esophageal microbiota in EC development and its treatment, and discuss the challenges in the clinical application of intestinal and esophageal microbiota.