Background: Many circulating microRNAs have been studied and analyzed for non-invasive prediction of hepatocellular carcinoma in HCV-infected Egyptians. However, both miR-106b and miR-198 have not received the adequate concern for research. Aim of study: The present study sought to create a novel model for diagnosis and predication of HCC using miRNA-106b and miR-198. Material & Methods: 100 patients with HCV-induced liver diseases and 32 normal volunteers as controls were included. The liver diseases include chronic hepatitis C (n = 32), liver cirrhosis (n=36), and HCC (n = 32). Real-time-PCR (qRT-PCR) used to asses serum microRNA-106b and microRNA-198 expression levels. Level of several traditional markers of liver function and ∝-fetoprotein were determined. Analysis data was determined using SPSS 20 and area under receiver operating characteristic curve utilized to assess variables diagnostic power. Results: The fold change of miR-106b expression (Median; IQR) was significantly (P < 0.0001) upregulated in HCC patients in comparison with LC patients and CHC patients. However, miR-198 expression was decreasing gradually with the progression of liver disorder from CHC to LC to HCC. The levels of AFP and other traditional HCC-associated markers showed significant differences (p < 0.05) between the investigated groups. The AUROC analysis showed that both miR-106b and miR198 had higher diagnostic values (AUROC = 0.920 and 0.888; respectively) than AFP (AUROC = 0.847) to differentiate between HCC and non-HCC subjects. Conclusion: miR-106b and miR-198 expression levels of can be utilized as non-invasive sensitive and specific biomarkers for early prediction of HCV-induced HCC in Egyptian patients.