Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. Methods: We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS)

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... d local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). Results: Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; p = 0.049) and RFS (42.5% vs. 29.8%; p = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; p < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; p = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; p < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; p = 0.035), RFS (45.0% vs. 27.0% RFS; p < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; p < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. Conclusions: Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.