When anti-PD-1 drugs target healthy tissues, it may cause immune-related adverse events (irAEs). Hematological toxicities and renal immune-related adverse reactions were rare; these events recorded were often clinically severe and life-threatening. In this study, we first reported on an elderly esophageal cancer (ESC) case of cytokine release syndrome (CRS) and irAEs induced by radiotherapy following anti-PD-1 drug treatment. A 69-year-old male patient with ESC was hospitalized on December 2, 2019, after three cycles of chemotherapy with docetaxel and nedaplatin accompanied by the addition of PD-1 inhibitor (Sintilimab). The chemotherapy scheme was interrupted due to the absence of any response. Instead, three-dimensional conformal radiotherapy (60 Gy/30 times, 5 times/week) was locally applied to treat the esophageal lesion. Typical CRS and irAEs, including mild diarrhea, intermittent low fever, and leukopenia, occurred after 6 times of radiotherapy, which was alleviated by symptomatic treatment. Such radiotherapy, however, encountered an unexpected early ending after 10 times with patient platelet level being significantly decreased to 31x10(9)/L and the serum creatinine of the patients sharply increased from 78.4 to 609.5 mu mol/L. CT scan presented scattered inflammation in both lung. It also showed that mediastinal lymph nodes and esophageal lesions were significantly reduced, and the patients received symptomatic treatment of glucocorticoids and other immunomodulators. The patient get discharged from the hospital after the combination treatment improved the irAEs symptoms. This paper showed the possibility of CRS and multiple-organ injuries as potential irAEs during radiotherapy following the anti-PD-1 therapy strategy and discussed the management of these adverse events (AEs).