This case report describes a life-threatening anaphylaxis to fentanyl during radiofrequency ablation (RFA). A 50-year-old woman with hepatocellular carcinoma was admitted for RFA. She denied any history of adverse drug reactions or past adverse anesthetic reaction. Physical examination, vital signs, any laboratory findings were all within normal limits. Ten minutes after intravenous administration of 50 mcg of fentanyl before starting RFA, she developed generalized erythema and sudden onset of bronchospasm followed by respiratory arrest. Cardiopulmonary resuscitation (CPR) commenced with 100% oxygen and intravenous administration of epinephrine 1 mg. After 5 minutes of CPR, she had the return of spontaneous circulation. Chest X-ray revealed pulmonary edema which resolved over two days. She recovered completely and was discharged home. After six weeks, intradermal tests performed with fentanyl, remifentanyl, midazolam, and profopol. Among those, only fentanyl induced positive skin response. Fentanyl induced anaphylaxis was diagnosed for this case, and fentanyl was avoided in the subsequent general anesthesia for liver transplantation. This case suggested that fentanyl could induce anaphylaxis combined with uncommon comorbidities like pulmonary edema.