The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171 per course while improving the rate of sustained virologic response (SVR) from 59-66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments ranged from $9724 to $29,189 per treatment success, which were all below the cost-effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection management over 5 years. A 50% change in DAA medication costs reflected a change in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs to the public hospital formulary yields a considerable budget increase but is still economically favorable to the local government.