The prognostic nutrition index (PNI), calculated based on serum albumin and lymphocyte counts, predicts the prognosis of several cancers, including operated esophageal cancers. In this study, we determined whether PNI could predict the occurrence of severe adverse events by chemotherapy and chemoradiotherapy, and overall survival in esophageal cancer. We collected data from 191 patients with esophageal cancer treated with at least one course of cisplatin and 5-fluorouracil from 2005 to 2016. We compared the incidences of severe adverse events and overall survival between a high- and a low-PNI group. The optimal cut-off value of the Onodera PNI was 43.2. Patients with low PNIs suffered more frequent severe adverse events than did those with high PNIs, and the latter patients survived longer. The PNI was independently prognostic of overall survival and stage. The PNI predicted the development of severe adverse events caused by chemotherapy or chemoradiotherapy, and overall survival, in esophageal cancer patients.