BackgroundBalloon catheter isolation is a promising auxiliary method for thermal ablation treatment of liver cancer. We aimed to explore the safety and effectiveness of balloon catheter isolation-assisted ultrasound-guided percutaneous microwave ablation (MWA) in treating liver cancer in difficult anatomical locations. MethodsData of 132 patients with 145 difficult-site liver cancer treated with ultrasound-guided percutaneous MWA were retrospectively analyzed. Participants were classified into the isolation (n = 40) and non-isolation (n = 92) groups based on whether the patients were treated using a balloon catheter prior to ablation. The major complication rates, local tumor residuals (LTR), and tumor follow-up for local tumor progression (LTP) at 6 and 12 months post-ablation were compared between the two groups. ResultsThe rates of major postoperative complications did not significantly differ between the isolation and non-isolation groups (2.5% vs. 4.3%, P = 0.609). The postoperative LTR rates were significantly different between the isolation and non-isolation groups (4.8% vs. 17.5%, P = 0.032). Balloon catheter isolation [odds ratio (OR) = 0.225, 95% confidence interval (CI): 0.085-0.595, P = 0.009] and tumor diameter (OR = 2.808, 95% CI: 1.186-6.647, P = 0.019) were identified as independent factors influencing LTR rate. The cumulative LTP rates at 6 and 12 months after ablation showed no significant differences between the isolation and non-isolation groups (2.6% vs. 7.9%, P = 0.661; 4.9% vs. 9.8%, P = 0.676, respectively). Cox proportional hazards regression analysis showed that tumor diameter was an independent risk factor for cumulative LTP rate (OR = 3.445, 95% CI: 1.406-8.437, P = 0.017). ConclusionsBalloon catheter isolation-assisted MWA was safe and effective in the treatment of difficult-site liver cancer. Additionally, tumor diameter significantly influenced LTR and LTP rates after ablation.