Background and Aims: For unresectable hilar cholangiocarcinoma, effective treatments should be performed to relieve the biliary obstruction, and thereby to improve the quality of life and survival rates of the patients. This study was aimed to investigate the application value of nanoknife ablation in treatment of unresectable hilar cholangiocarcinoma through comparison of the efficacy and safety between nanoknife ablation combined with percutaneous transhepatic cholangial drainage (PTCD) and PTCD alone for unresectable hilar cholangiocarcinoma, so as to provide the basis and reference for the treatment selection of the condition.  
Methods: Thirty-five patients with unresectable hilar cholangiocarcinoma admitted in the Fifth Affiliated Hospital of Zhengzhou University from July 2016 to July 2017 were designated to observation group (15 cases) and control group (20 cases). Patients in observation group underwent nanoknife ablation 1 to 2 weeks after PTCD treatment, and patients in control group underwent PTCD alone. The changes in the levels of transaminases and total bilirubin (TBIL), scores for quality of life and postoperative survival rates were compared between the two groups of patients before and after treatment, and the recanalization of the bile duct as well as the adverse reactions and complications in the patients after nanoknife ablation treatment, and the incidence of rehospitalization due to internal PTCD tube obstruction and infection in patients undergoing PTCD alone were observed. 
Results: There were no significant differences in the general data and liver function parameters between the two groups of patients (all P>0.05). The levels of transaminases and TBIL, and scores for quality of life at 1 and 3 months after operation were significantly improved compared with those before operation in observation group (all P<0.05), which were significantly improved at 1 month after operation (all P<0.05), but showed no significant difference at 3 months after operation compared those before operation in control group (all P>0.05). All above variables in observation group were significantly superior to those in control group at both 1 month and 3 months after operation (all P<0.05). The median survival time in observation group was significantly longer than that in control group (15 months vs. 5 months, P<0.05.), and the 1-year survival rate in observation group was significantly higher than that in control group (80.0% vs. 15.0%, P<0.05), but the 2-year survival rates showed no significant difference between the two groups (6.7% vs. 0, P>0.05). In observation group, the removal rates of PTCD tube were 82.6% and 98.0% at 1 and 3 months after operation, and the patency time of the bile duct was (185.1±95.8) d; the discomfortable symptoms such as abdominal distention and fever occurred in some patients, biliary infection occurred in 2 cases and upper gastrointestinal hemorrhage occurred in 1 case. In control group, the rates of rehospitalization due to PTCD tube obstruction or infection was 50%. 
Conclusion: Nanoknife ablation has demonstrable efficacy in treatment of unresectable hilar cholangiocarcinoma, which can effectively improve the liver function, prolong the survival time of the patients, and also can recanalize the bile duct, then provide the patients an opportunity for drainage tube removal, thereby improve the patients’ quality of life, with a high safety. It offers a new treatment modality for patients with unresectable hilar cholangiocarcinoma.