Objective: Hepatocellular carcinoma (HC) ranks as the 5th most common malignant cancer and the 3rd most frequent cause of death worldwide. The majority of HCC patients are not amenable to curative therapy as they are detected at late stages. Therefore, our aim was to evaluate the clinical implications of TNF-α level and its correlation with the activities of GGT and LDH in monitoring the progression of HCV-chronic liver disease.  Materials and methods: This study comprised forty eight patients suffering from HCV-chronic liver disease; 24(50%) cases with HCC, 14(29.2%) cases with LC and 10(20.8%) cases with CH. Twenty five healthy individuals (HI) served as control group. Sera of all individuals were examined for the activities of TNF-α, LDH, GGT, AFP and its correlation with other laboratory investigations.  Results: Serum levels of TNF-α, LDH, AFP were elevated significantly in HCC patients compared to LC and CH but the difference between LC and CH was elevated significantly only (p<0.0001) in TNF-α. Significant association was recorded between LDH and TNF-α, GGT, AFP, ALT and ASTlevels. Linear regression for TNF-α, LDH and AFP showed significant prediction for progression of HCV-chronic liver disease. Conclusion: Serum level of LDH and TNF-αcould be used simultaneously with AFP for the evaluation of chronic inflammation leading to cancer development.