Recently, there is a widespread usage of anti-hepatitis C drugs in the world where the disease is classified as epidemic and life threatening. Direct-acting antivirals drugs, (DAAs), are introduced as promising medication regimens to treat chronic HCV infection. From the clinical point of view, it is necessary to introduce reliable method for the determination of the three new drugs: Daclatasvir (DAC); Sofosbuvir (SOF); and Ledipasvir (LED). For the first time a simple, reliable, time efficient, direct and ultrasensitive sensor is designed for the determination of DAAs. The sensor is constructed by applying a thin layer from a mixture of multi-walled carbon nanotubes-ionic liquid crystal to glassy carbon electrode-surface followed by electrodeposition of cobalt nanoparticles (GC/(CNTs-ILC)/Co). The sensor exhibited excellent electro-catalytic activity toward LED, DAC and SOF determinations in human serum in wide linear dynamic ranges. The detection limits for LED, DAC and SOF were found as: 0.277 nmol L-1, 1.86 nmol L-1 and 7.29 nmol L-1 respectively. The GC/(CNTs-ILC)/Co sensor has been applied for the simultaneous determination of LED with SOF and in presence of interfering compounds. Furthermore, the application was extended to analysis of combination from LED and SOF in its pharmaceutical formulation. (C) 2018 The Electrochemical Society.