Researchers analyzed the effectiveness and safety of direct-acting antivirals (DAAs) in patients with curative or active hepatocellular carcinoma (HCC) vs to patients without HCC. For this prospective cohort study, they consecutively recruited 713 Taiwanese patients who received standard-of-care DAAs. The overall rate of sustained virological response (SVR12) was 96.9%. The SVR12 rate was similar between HCC and HCC-free patients. Patients with viable HCC had a significantly higher proportion of serious adverse events, early discontinuation of treatment, and mortality vs patients with curative HCC. In patients with either past or active HCC, an equivalently high rate of SVR was seen vs those without HCC. The safety concerns in patients with HCC did not impair the effectiveness of treatment.