Chemoradiation therapy (CRT) for esophageal cancer induces inflammatory responses within tumor tissues. Inflammatory cells infiltrated into the tumor tissues may modulate the CRT responses via inflammation-related molecules such as IL-6 or COX-2. In the present study, we investigated a relationship between IL-6/COX-2 expression and CRT responses for esophageal cancer. A surgical resection following CRT was performed, and the specimens from the patients with cT3/T4 esophageal squamous cell examined for IL-6/COX-2 expression in both residual cancer and stromal cells by immunohistochemical staining. CRT responses were divided into responder group (Grade 1b and Grade 2) and non-responder group (Grade 1a). COX-2 in cancer cells and IL-6 in stromal cells were associated with non-responder and responder, respectively. In addition, IL-6 in stromal cells was significantly correlated with overall survival. Our data suggest that inflammatory responses concomitant with CRT responses could play a role in chemoradiation responses and prognosis.