In recent years,direct-acting antiviral agent( DAA) that target specific enzymes in the life cycle of hepatitis C virus( HCV)have been developed rapidly. However,there are specific resistance-related mutation sites for DAA,which is associated with the gene types / subtypes of HCV. This article describes the resistance-related mutation sites for DAA and their impacts on the treatment regimen according to the mechanism of action of DAA. It is pointed out that some natural mutation sites lead to drug resistance in the treatment for patients with some HCV subtypes,so careful evaluation is needed before treatment to determine the appropriate regimen. For patients experiencing failure in the previous interferon therapy,the pre-existing drug resistance should be studied if DAA in combination with the therapy or interferon-free DAA therapies are to be used.