Iron homeostasis is of critical for human life. The pathogenesis of its accumulation in chronic hepatitis C (CHC) virus is not yet completely understood.  Objectives: The aim is to investigate the possible correlations between serum metabolic markers of iron, HCV viral load, total micro-RNA-cDNA and the progression of liver disease into hepatocellular carcinoma (HCC). Patients and methods, A total of 126 patients with chronic hepatitis C virus were included in this study. Of them 22 patients were with HCC and 44 were CHC patients without HCC. In addition, a group of 30 healthy individuals were included and was served as control group. RNA was extracted and total microRNA was converted into-cDNA and was determined by nanoQuant, iron status with standard assay techniques. HCV antibodies were evaluated by enzyme linked immunosorbent assay (ELISA) and HCV-RNA by real time polymerase chain reaction (RT-PCR). Alpha-fetoprotein, routine liver function tests, international normalization ratio (INR) and platelets count were also done. Beside, HCV-related HCC were radiologically proved via abdominal US and Triphasic abdominal CT. Results:  Markers of iron metabolism; including iron and ferritin were dramatically increased in sera of HCC patients compared with those of the non-HCC group. Conversely,   the mean TIBC level was highly reduced in sera of HCC patients^, group compared with that of the non-HCC individuals. Significant and positive correlations were found between the individual levels of iron markers with serum liver enzymes and bilirubin. On the other hand, negative correlations were found between the levels of these markers with both albumin and platelets, especially in the blood of HCC patients. Total miRNA-cDNA and viral RNA showed no significant difference among the two groups but the level of the former was significantly lowered in sera of HCC patients compared with those of the control group. In conclusion, these results suggest that serum markers of iron mediate liver disorders; especially HCC and can represent surrogate markers for the severity of such disorders. Also, the role viral molecules and/or micro-RNA in iron overload must not be neglected.