Purpose: The purpose of this study was to evaluate the feasibility, safety and efficacy of percutaneous ablation (PA) of obscure hypovascular liver tumors in challenging locations using arterial CT-portography (ACP) guidance.Materials and methods: A total of 26 patients with a total of 28 obscure, hypovascular malignant liver tumors were included. There were 18 men and 6 women with a mean age of 58±14 (SD) years (range: 37-75 years). The tumors had a mean diameter of 14±10 (SD) mm (range: 7-24mm) and were intrahepatic cholangiocarcinoma (4/28; 14%), liver metastases from colon cancer (18/28; 64%), corticosurrenaloma (3/28; 11%) or liver metastases from breast cancer (3/28; 11%). All tumors were in challenging locations including subcapsular (14/28; 50%), liver dome (9/28; 32%) or perihilar (5/28; 18%) locations. A total of 28 PA (12 radiofrequency ablations, 11 microwave ablations and 5 irreversible electroporations) procedures were performed under ACP guidance.Results: A total of 67 needles [mean: 2.5±1.5 (SD); range: 1-5] were inserted under ACP guidance, with a 100% technical success rate for PA. Median total effective dose was 26.5 mSv (IQR: 19.1, 32.2 mSv). Two complications were encountered (pneumothorax; one abscess both with full recovery), yielding a complication rate of 7%. No significant change in mean creatinine clearance was observed (80.5mL/min at baseline and 85.3mL/min at day 7; P=0.8). Post-treatment evaluation of the ablation zone was overestimated on ACP compared with conventional CT examination in 3/28 tumors (11%). After a median follow-up of 20 months (range: 12-35 months), local tumor progression was observed in 2/28 tumours (7%).Conclusion: ACP guidance is feasible and allows safe and effective PA of obscure hypo-attenuating liver tumors in challenging locations without damaging the renal function and with acceptable radiation exposure. Post-treatment assessment should be performed using conventional CT or MRI to avoid size overestimation of the ablation zone.