Abstract Introduction/Objective MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs which are make a contribution in the regulation of gene expression and protein translation, and they play vital roles in differentiation, cell growth, and the development of diverse types of cancers. Methods/Case Report Our research was done in hepatology and gastroenterology department at the National Liver Institute, Menoufia University. It included 135 patients and 60 healthy subjects serving as control group. We have 3 groups: Group I (Control) This group included 60 apparently healthy individuals. They were 32 males and 28 females, whose ages ranged from 39 to 67 years old (mean ±SD= 51.67 ± 6.40 years). Group II (Cirrhosis) This group included 75 patients with liver cirrhosis due to chronic HCV infection. They were 41 males and 34 females whose ages ranged from 41 to 68 years old (mean ±SD= 54±6.73 years). Group III (HCC) Sixty patients with HCC were included. They were 35 males and 25 females, whose ages ranged from 41 to 70 years old (mean ±SD= 53.97±6.15 years). Laboratory Investigations Complete blood count (CBC), Liver tests: aspartate transaminase (AST) and alanine transaminase (ALT), serum albumin, total and direct bilirubin, alkaline phosphatase and INR were measured. Serum creatinine was also measured. The analysis of serum alpha fetoprotein (AFP) (ng/ml) was done. Chronic HCV infection was diagnosed by detection of HCV antibody and HCV RNA by real time PCR. Anti-HCV antibody was detected by means of a third generation enzyme immunoassay. Quantification of HCV RNA level was performed by means of COBAS Taqman 84 (Roche) real time HCV RNA Assay with lower detection limit 15 IU/ml. Results (if a Case Study enter NA) In control group, miRNA-215 ranged from 1.60 to 21.30 with a median value of 6.89. In cirrhotic patients group, it ranged from 0.70 to 14.65 with a median value of 2.85. In patients with HCC group, it ranged from 0.03 to 10.95 with a median value of 0.52 (pg/ml). MiRNA-215 and AFA mean levels showed a statistically significant difference (p <0.001) between the three studied groups. Conclusion In conclusion, MicroRNA-215 was proved to be significantly lower in HCC patients compared to cirrhotic patients and control group. This marker might be used as a potential serologic marker for HCC and a complementary diagnostic tool in monitoring cirrhotic patients for detection of HCC.