Context: Hepatitis C virus (HCV) infection is a significant cause of chronic liver disease in patients with human immunodeficiency virus (HIV) infection. Introduction of HCV direct-acting antiviral agents (DAAs) revolutionized the treatment of hepatitis C in patients with HIV/HCV co-infection. In this study, we systematically reviewed the treatment of chronic HCV infection in patients with HIV/HCV co-infection. Evidence Acquisition: In this systematic review, electronic databases including PubMed, Scopus, ScienceDirect, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "HCV", "HIV" and "DAA". Studies assessed the effectiveness of interferon-free HCV antiviral therapies in patients with HIV/HCV co-infection were evaluated for inclusion in the systematic review. Results: After the screening of 728 records, we included 33 articles in our study, and seven different HCV antiviral regimens were evaluated. Ten studies for sofosbuvir plus simeprevir (SVR ranged from 72.2% to 100%), eight studies for sofosbuvir plus ribavirin (SVR ranged from 51.6% to 91.6%), 12 studies for sofosbuvir/ledipasvir (SVR ranged from 88.8% to 100%), eight studies for sofosbuvir plus daclatasvir (SVR ranged between 84.6% and 100%), two studies for grazoprevir/elbasvir (SVR ranged from 86.6% to 96.5%), six studies for ombitasvir/paritaprevir/ritonavir plus dasabuvir (SVR ranged from 90.6% to 100%), and just one study for sofosbuvir/velpatasvir with 95.2% SVR rate. Conclusions: This study found that treatment of HCV infection with DAAs can result in high SVR rate in patients with HIV/HCV co-infection.