Esophageal perforation (EP) is a rare disease mostly caused by iatrogenic endoscopic procedures.Esophageal cancer accounts for ten percent of them, and EP under such circumstance could be more complicated and often leads to poor outcome. Therefore, early recognition is of vital importance to prolong survival. To our knowledge, this is the first case report to propose the possible role of transcatheter arterial embolization (TAE) in EP. A 58-year-old female with stage III esophageal cancer (cT3N1M0) was presented to our emergency room. Four months before, she had received TAE because of tumor bleeding and then underwent neoadjuvant concurrent chemoradiotherapy (CRT) after recovery. Prior completion of CRT, dizziness, vomiting, chest tightness and chest pain developed. On examination, fever up to 38.8 degrees was found, accompanied with increased infiltration over the bilateral lungs on the chest radiograph. Under the initial impression of pneumonia, she was first managed with antibiotics and fluid hydration. However, drop of blood pressure occurred six hours later and emergent computed tomography of chest revealed pneumomediastinum and pericardial effusion. Upper gastrointestinal endoscopy showed severe mucosal breakage and EP was confirmed. Broad-spectrum antibiotics and fluid resuscitation were subsequently initiated. Pericardial window was also performed due to cardiac tamponade and the bacterial culture from the mediastinal fluid yielded Pseudomonas aeruginosa. Placement of metal stent was advised but refused by her family. With supportive care only, the patient died one month later due to progressive sepsis and multiorgan failure. EP may occur during CRT if there are risk factors such as T4 primary tumor, age more than 60 or extracapsular lymph node that involves the esophagus. In our case, we thought previous TAE is another factor that possibly contribute to the EP via generation of ischemia and alteration of healing microenvironment. In this setting, risk of EP should be carefully evaluated when subsequent CRT is attempted.