Background & aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) after successful treatment of early hepatocellular carcinoma (HCC) has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation.Methods: We enrolled prospectively 163 consecutive patients with HCV-related cirrhosis and at first diagnosis of early Barcelona Clinic Liver Cancer (BCLC) 0/A HCC who had achieved a complete radiologic response after curative resection or ablation, subsequently treated with DAAs. DAA-untreated patients from ITA.LI.CA. cohort (n = 328) served as controls. After propensity-score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared.Results: In DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in DAA group compared with No DAA group (hazard ratio [HR] = 0.39; 95% confidence Interval [CI] = 0.17–0.91, p = 0.03). HCC recurrence was not significantly different between DAA and No DAA groups (HR = 0.70; 95%CI = 0.44–1.13, p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in DAA group compared with No DAA group (HR = 0.32; 95%CI = 0.13-0.84, p = 0.02). In DAA group, sustained virologic response was a significant predictor of overall survival (HR 0.02, 95%CI 0.00–0.19, p < 0.001), HCC recurrence (HR 0.25, 95%CI 0.11–0.57, p < 0.001) and hepatic decompensation (HR 0.12, 95%CI 0.02-0.38, p = 0.02).Conclusions: In patients with HCV-related cirrhosis and previous successful treatment of early HCC, DAAs significantly improved OS compared with No DAA treatment.