This present study was aimed to assess the effectiveness and reliability of CT-guided nanoknifeablation in retroperitoneal tumor treatment. Methods: 2 retroperitoneal tumor patients were selected, includingone pancreatic cancer patient and one colorectal cancer retroperitoneal metastatic tumor patient. The surgery wasperformed under general anesthesia with large aperture multi-slice CT, electrocardio synchroscope and anesthesiamonitoring device. Nanoknife ablation electrode was implanted through percutaneous conformal puncture in ac-cordance with preoperative plan and ablation degrees were estimated by current waveform. It was significant toperform CT examination immediately to eliminate complications and monitor patients vital signs continuously andcomprehensively after surgery. Imaging test was implemented to observe curative effects and complications 3-5days after surgery and each laboratory examination of blood needed to be reviewed. Results: 2 cases of surgerywere completed successfully and the vital signs of patients were stable. Pancreatic cancer patient underwent mildabdominal pain without any severe complications after surgery. Imaging test displayed complete ablation, clearborder, no intensification in ablation area, mild inflammatory change around and no damages on nearby blood ves-sels, biliopancreatic ducts and intestinal canals. The pancreatic cancer patient showed transient rises of lipase anddiastase and mild rise of tumor marker via laboratory examination. There was no abnormality in laboratory indexof retroperitoneal metastasis patient. Conclusion: Nanoknife ablation could protect blood vessels, biliopancreaticducts and intestinal canals while inactivating tumors in the process of retroperitoneal tumor ablation. This tech-nique was safe and effective, which might be further popularized and applied clinically.