〔Abstract〕 Objective To investigate whether serine/threonine kinase 3(AKT3)is able to reverse the synergistic inhibition of miR-22-3p/29a-3p on the activation of human hepatic stellate cell LX-2. Methods TargetScan, Starbase, miRDB and DIANA were used to predict the common target genes of miR-22-3p and miR-29a-3p, and the selected target genes were analyzed by Kyoto encyclopedia genes and genomes(KEEG),gene ontology(GO), protein-protein interaction(PPI). The binding free energy of candidate target genes with two miRNAs was analyzed by RNAhybrid, and their targeting relationship was determined by double luciferase reporting experiment. CCK-8, Transwell and qRT-PCR were used to detect the proliferation, migration and the expression of fibrosis markers of LX-2 cells. Results There were 24 common target genes of miR-22-3p and miR-29a-3p, and they were enriched in the hepatic fibrosis-related signaling pathways and biological processes. The binding free energy analysis of candidate target gene AKT3 with miR-22-3p and miR-29a-3p combined with the double luciferase experiment results showed that AKT3 was the common target gene of miR-22-3p and miR-29a-3p. The proliferation, migration and the mRNA expression of fibrosis markers of α-smooth muscle actin(α-SMA) and type I collagen α1 chain(COL1A1) of LX-2 cells were inhibited by miR-22-3p and miR-29a-3p mimics independently or cooperatively(P<0.05), and AKT3 overexpression could reverse the synergistic inhibition of miR-22-3p and miR-29a-3p mimics on LX-2 cells mentioned-above(P<0.05).Conclusion The overexpression of AKT3 can reverse the synergistic inhibition of miR-22-3p and miR-29a-3p on the activation of LX-2 cells.