Introduction: The targeting of hepatocellular carcinomas (HCC) in the hepatic dome can be challenging during percutaneous thermal ablation (PTA). The aims of this study were (1) to evaluate the safety and efficacy of PTA of HCC in the hepatic dome that cannot be visualized under US, using artificial CO2 pneumothorax and CT-guidance and (2) to compare the results with US-visible HCC located in the liver dome treated under US-guidance. Materials: Over a 32-month period, 56 HCC located in the hepatic dome were extracted from a prospectively maintained database. Twenty-eight cases (US-guidance group) were treated under US-guidance, while the others (n = 28, CT-CO2 group) were treated under CT-guidance using artificial CO2 pneumothorax after lipiodol tagging of the tumor. The primary technical success and complications rates of this technique were retrospectively assessed. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), local recurrence-free survival (LRFS) and overall survival (OS) were also compared between both groups. Results: Primary technical success was 100% in both groups. No major complications occurred. After a median follow-up of 13.8 months (range, 1–33.4 months), LTP occurred in 10.7% (3/28) in CT-CO2 vs. 25% (7/28) in the US-guidance group (p = NS). IDR occurred in 39.3% (11/28) in CT-CO2 vs. 28.6% (8/28) in the US-guidance group (p = NS). Death occurred in 17.9% (5/28) of patients in both groups. LRFS and OS did not significantly differ using Kaplan-Meier survival estimates. Conclusion: CT-guided PTA after artificially induced CO2 pneumothorax is a safe and efficient technique to treat HCC located in the hepatic dome.