Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and Tcell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis, and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct-acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response. Indeed, curing HCV infection with an oral medication is now reality. The effects of DAAs inmitigating the HCV-related complications of liver fibrosis and cancer are yet largely unknown. Nonetheless, recent controversial reports suggest a potential increase in liver cancer recurrence upon use of DAAs. In the current article, we review the most important immunemediated mechanisms underlying HCV chronicity and the development of liver fibrosis and cancer. Furthermore, we discuss recent concern on use of the new agents.