Hepatitis C virus (HCV) infects primarily hepatocytes, leads to development of fibrosis and/or cirrhosis of the liver and is a significant factor for developing hepatocellular carcinoma (HCC). Evidence indicates that liver fibrosis contains uncontrolled inflammation as a part of its etiology. Normal cell-mediated immunity plays a central role in the mechanisms involved in viral clearance/persistence in the liver. In this context, cytokines modulate the immune system and exert direct anti-viral activity. To this end, this study investigated potential associations of serum IL-17 and IL-6 with exacerbation of hepatic damage in chronic HCV patients to determine their utility as prognostic markers for potential development of HCC. Chronic HCV-patients were recruited, divided into groups according to degree of liver damage, i.e. patients with peri-hepatic fibrosis, hepatic cirrhosis, or HCC, and had their blood collected for analysis of liver function and serum IL-6 and IL-17 levels. Interestingly, increases in serum IL-17 levels in the study groups were associated with aggravation of the clinical state from HCV to cirrhosis and then to HCC. Serum IL-6 levels followed a similar pattern. The association of both cytokines with progressive exacerbation of the initial HCV-induced liver damage was further confirmed by correlation analysis that revealed positive correlations between HCV RNA titer and IL-17 (+0.951, p < 0.05) and IL-6 (+0.85, p < 0.05). A receiver operating characteristics (ROC) analysis revealed their beneficial addition as promising biomarkers for a better prognostic profile of HCC. Interestingly, a significant progressive decline in the active vitamin D status was noted in all three clinical states, and these too were associated with progressive liver disease. This study confirms the necessity of adding screening for IL-6 and IL-17 and vitamin D to that of the classic marker AFP for patients with HCV and cirrhosis to hopefully permit clinicians to initiate measures that ultimately might mitigate/delay development of HCC in these infected patients.