Objective: To compare the therapeutic efficiency and risk of intraoperative cryoablation therapy (IOCT) and intraoperative combined cryoablation and hyperthermia (ICCH) in the treatment of unresectable pancreatic cancer. Methods: Patients with unresectable pancreatic cancer admitted to the Pancreatic Center of the Second Affiliated Hospital of Nanjing Medical University were divided into two groups: IOCT group (101 cases) and ICCH group (35 cases). The clinical data of patients were analyzed and surgical methods were compared. The incidence of postoperative complications, survival rate, tumor indexes and pain scores were compared in groups. Results: Compared with IOCT group, the intraoperative blood loss was less in ICCH group (P < 0.01). The postoperative fasting time in ICCH group was shorter than that in IOCT group (P < 0.01). The incidence and severity of postoperative complications in ICCH group were lower than those in IOCT group (P < 0.05). The 1-year survival rate of patients with pancreatic head carcinoma was significantly higher in ICCH group than in IOCT group (P = 0.034). Conclusion: ICCH is more effective in the treatment of unresectable pancreatic cancer, with lower risk and lower complication rate than IOCT.