Background and AimThis study aimed to investigate the survival outcomes of antiviral agents (direct‐acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma.MethodsThis retrospective single‐center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence‐free survival (RFS), and risk factors were analyzed.ResultsAfter a median follow‐up time of 50.4 months, the rates of 5‐year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty‐eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242–0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637–7.017; RFS HR 2.594, 95% CI: 1.520–4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007–0.991) were protective against hepatic decompensation events but not recurrence events.ConclusionIn patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.