Methods and compositions for the efficient and accurate determination of susceptibility of a hepatitis C virus (HCV) or HCV population to an HCV inhibitor. The inhibitor may include, for example, an interferon (IFN), ribavirin (RBV), one or more nucleos(t)ide inhibitors, including for example nucleoside inhibitor-1 (NI-1), 2&prime；C-methyl adenosine (2&prime；CMeA), sofosbuvir (SOF), or non-nucleoside inhibitor targeting site A or B (NNI-A or NNI-B) are provided. The methods may involve determining the genotype of the HCV or the phenotype of the HCV with respect to the inhibitor susceptibility. The methods may further include the selection of a suitable treatment based on the genotype or phenotype determined.
