Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is the frequent reason for cirrhosis all over the world. MicroRNA could be used as a disease biomarker. This investigation was carried out to investigate mRNA -125b, mRNA 489-3p, and biochemical analysis as markers for chronic HBV. This work included 20 patients who had chronic liver disease admitted to the Gastroenterology Hospital and Oncology Institute in Mansoura. After investigation, serum samples were obtained from five patients that were positive for PCR chronic HBV. For control, negative serum samples were collected at the same age range and sex. Liver function and alpha fetoprotein (AFP) parameters were estimated. RNA was extracted from serum for gene expression of mRNA125b and mRNA 489-3p. The main results showed that the HBV group had a significant increase in ALT, AST, TBIL, GGT, ALP, and AFP, while there was a significant decrease in albumin levels compared to the control group. HBV group showed a significant increase (6.70 ± 0.18) in mRNA125b, but a significant decrease in mRNA489-3 (0.51±0.03). In conclusion, mRNA125b and mRNA489-3p expressio