Around 170-200 million individuals have hepatitis C virus (HCV), which represents similar to 3% of the world population, including similar to 3-5 million people in the USA. According to the WHO regional office in the Middle East, Egypt has the highest prevalence in the world, with 7% prevalence in adults. There had been no effective vaccine for HCV; a combination of PEG-Interferon and ribavirin for at least 48 weeks was the standard therapy, but it failed in more than 40% of the patients and has a high cost and serious side effects. The recent introduction of direct-acting antivirals (DAA) resulted in major advances toward the cure of HCV. However, relapse and reduced antiviral efficacy in fibrotic, cirrhotic HCV patients in addition to some undesired effects restrain the full potential of these combinations. There is a need for new approaches for the combinations of different DAA and their targeted delivery using novel nanotechnology approaches. In this review, the role of nanoparticles as a carrier for HCV vaccines, anti-HCV combinations, and their targeted delivery are discussed.