Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies show that microRNAs (miRNA) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. To detect the miRNAs expression profiling and to screen the differentially expressed miRNAs in patients with HBV-related liver fibrosis, the whole blood was collected from the HBV-related liver fibrosis patients (F2/3, n=10) based on Scheuer’s staging criteria. In addition, healthy volunteers (n=8) served as the control group. The expression of plasma miRNAs was detected by IlluminaHiSeq sequencing. Cluster analysis and target genes prediction of differentially expressed miRNAs were carried out. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of differentially expressed miRNAs target genes were performed. Compared with the healthy control group 104 miRNAs were screened out from the liver fibrosis group, among which 72 miRNAs were up-regulated and 32 were down-regulated. Pathway annotations for the target genes of the miRNAs identified were found that it participated in many signal pathways including MAPK signaling pathway, TNF signaling pathway, Notch signaling pathway, phosphatidylinositol signal system and so on. According to the bioinformatic analysis，miR-98-5p were selected for function research among the differentially expressed miRNAs.MiR-98-5p prevents liver fibrosis by targeting TGFβR1 and blocking TGFβ1/Smad3 signaling pathway. In addition, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. We found that serum miR-98-5p level was significantly lower in patients with live fibrosis than in healthy controls and HBV carriers (P<0.05). Those results suggest that miR-98-5p could be a potential therapeutic target for liver fibrosis .