Esophageal cancer (EC) is the ninth most common malignancy with a poor prognosis. It is clear that improvements need to be made to reveal the exact molecular mechanisms of EC. Cancer-related inflammation (CRI) recently has been proposed as a major physiological hallmark of malignancy and has important value in diagnosis, treatment, and prognosis. But the role of CRI in EC has remained unclear. In this review, we focus primarily on the function of key mediators of CRI in EC, including transcription factors, chemokines, cytokines, reactive oxygen species, COX-2, and specific microRNAs. Through a comprehensive analysis, we try to reveal the interaction between CRI and EC, providing novel preventive, diagnostic, and therapeutic strategies to reduce the health burden of EC.