Hepatitis virus, an RNA virus belonging to the Flaviviridae family, is closely related to liver disease, which in 70–80% of patients becomes chronic, resulting in major complications such as cirrhosis and, in the year, also liver cancer. The antiviral activity of HCQ on the hepatitis C virus (HCV) in monotherapy has not been tested. However, it seems that this drug increases the antiviral effect of standard drugs. In a study including 120 Egyptian patients infected by the hepatitis C virus, it was seen that the combination of HCQ with pegylated interferon and ribavirin could improve biochemical and virological responses in chronic hepatitis C subjects. All patients were randomized and divided into two groups; the control group treated with standard-of-care (SOC) consisted of 160 µg of subcutaneous pegylated interferon and 1000–12000 mg/day of oral ribavirin, and the group treated with 200 mg HCQ plus SOC. At the end of the treatment (12 weeks), patients of HCQ + SOC group showed a high virological response compared to the control group (54/60 (90%) vs. 43/60 (71.7%); p = 0.011). Moreover, in the HCQ + SOC group, there was a normalization of ALT levels, as is also demonstrated by the earlier biochemical response (EBR) highlighted in HCQ + SOC group 58/60 (96.7%) than SOC group 42/60 (70%) [30]. These results were confirmed by several case reports regarding patient treatment with Porphyria Cutanea Tarda and Hepatitis C. It was seen that a low dose of HCQ (100 mg twice weekly) prevented the recurrence of Porphyria Tarda and reduced the viral response during HCV therapy, including ribavirin and interferon [45]. Furthermore, in a patient with chronic hepatitis and rheumatoid arthritis, a low risk for hepatitis virus reactivation was observed after treatment with steroids (< 7.5 mg/day), HCQ or sulfadiazine [46] in combination with antivirals as prophylaxis [47,48].