Objective To summarize the perioperative complications and anesthesia management experience of patients with pancreatic cancer who underwent nanoknife ablation. Methods A descriptive case series study was conducted to retrospectively analyze the clinical data of 31 pancreatic cancer patients who underwent nanoknife ablation. Their basic information and anesthetic management strategies were collected. The primary outcomes were the incidences of hypertension, hypotension, tachycardia and arrhythmia. The secondary outcomes included the percentages of maximum increases and decreases in systolic blood pressure (SBP) and diastolic blood pressure (DBP), the percentages of maximum increases and decreases in heart rate, the use of vascular active agents during surgery, the Visual Analogue Scale (VAS) scores at rest and during movement at postoperative 24 h, and the length of postoperative and total hospitalization stay. Results These patients had a mean age of (59±10) years old, where 24 patients were American Society of Anesthesiologists (ASA) Ⅱ grade and 7 patients were ASA Ⅲ. The most common preoperative comorbidity was hypertension (38.7%). The common symptoms included abdominal pain (64.5%) and abdominal distension (35.5%), and 80.4% of tumors were located at the head and neck of the pancreas. All the patients underwent surgery under general anesthesia and celiac plexus block was conducted during surgery, where thoracic paravertebral block was additionally applied in 3 patients and epidural anesthesia was also applied in 2 patients. During the ablation period, 77.4% of patients presented hypertension, 80.6% had hypotension, 58.1% had both hypertension and hypotension, 51.6% required vasopressors, 67.7% required antihypertensive drugs, 35.5% showed transient tachycardia, and 9.7% had transient arrhythmia. Compared with those before anesthesia, the percentage of maximum increases in SBP, DBP and heart rate during ablation was 10.1% [95% confidence interval (CI) 2.4%, 17.9%], 12.9% (95%CI 4.5%, 21.4%), and 19.2% (95%CI 11.5%, 27.0%), respectively; and the percentage of maximum decreases in SBP, DBP and heart rate during ablation was −36.0% (95%CI −40.9%, −31.0%), −32.1% (95%CI −37.1%, −27.1%), and −28.7% (95%CI −32.6%, −24.7%), respectively. The average anesthesia time was (305±69) min, and the operation time was (266±69) min. Tracheal tubes were removed in the operating room and all the patients returned to the ward safely. The VAS scores were (2.5±1.1) at rest and (4.2±1.8) during movement at postoperative 24 h. The length of postoperative and total hospitalization stay was (11±5) d and (16±6) d, respectively Conclusions The incidences of perioperative hypertension and hypotension are high for pancreatic cancer patients undergoing nanoknife ablation, and transient arrhythmia may occur. During ablation, deep muscle relaxation, electrocardiogram synchronization mode, and multi-mode analgesia are essential for perioperative management.