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Background/purpose The treatment of chronic hepatitis C (CHC) has evolved from interferon (IFN)-based therapy to direct acting antivirals (DAAs). The effect of antiviral treatment on outcome of hepatocellular carcinoma (HCC) patients with CHC has not been well analyzed in Taiwan. Methods From April 2015 to May 2018, 199 HCC patients with CHC undergoing DAAs treatment, including 127 having prospectively longitudinal observation, were enrolled. Among them, 107 BCLC 0/A patients achieving curative treatment of HCC were further compared with a historical cohort of 42 HCC patients experienced pegylated interferon (Peg-IFN) plus ribavirin for CHC after curative treatment. Results The sustained virological response (SVR) rates were 95.0% in BCLC stage 0/A (114/120), 97.1% in BCLC B (68/70), and 77.8% in BCLC C (7/9). The median recurrence-free survivals (RFS) between the DAA and IFN arms were of no difference by counting either from antiviral treatment (29.3 mo vs 39.2 mo, p = 0.764) or from curative treatment (65.8 mo vs 44.0 mo, p = 0.130), respectively. Achievement of SVR was the key independent factor associated with RFS and overall survival. The pattern of recurrence was also similar between the DAA and IFN arms. For intermediate stage HCC patients, the median time to tumor progression was 9.2 months from the initiation of DAA therapy, and 90% of patients maintained in BCLC B till 12 months after the DAA treatment. Conclusions The SVR is high within BCLC B HCV-HCC patients by DAAs treatment. The risk of HCC recurrence and progression is not increased by DAAs.