T helper (Th) cytokines play a key role in the immunological aspects of hepatitis C virus (HCV) pathogenesis. The pattern of Th1 (IL-2, interferon (IFN)-γ), Th2 (IL-10), and immunomodulatory cytokines (IL-12, IL-1β, IFN-α and tumor necrosis factor-α receptor (TNF-αR2) balance participated in the outcome of host immune responses. The study aimed to investigate the serum levels of Th1/Th2 and immunomodulatory cytokines in HCV infected patients in both genders during various liver disease stages compared to healthy controls. Blood samples were collected from 16 healthy individuals and 77 patients at different disease stages including chronic, cirrhosis, and hepatocellular carcinoma (HCC). Serum cytokine levels were measured by ELISA. Levels of serum IL-12 and IL-10 were significantly higher in both genders in all groups than those in corresponding healthy subjects. Whereas, HCV infected female patients showed significantly lower levels of IL-2, IL-1β, IFN-α in chronic and cirrhosis stages than corresponding males. The serum level of IFN-γ could be utilized as a biomarker for early detection of HCC. Finally, cytokine response variation in gender during various stages of the disease, implying that the subsequent activation and attenuated functional immune responses displayed differences in the balance of Th1 and immunomodulatory related cytokines between females and males upon infection.