AIM:To determine the effect of microRNA-363(miR-363) on HepG2 cells.METHODS:Bioin-formatic analysis was conducted to identify if the Mcl-1 was regulated by miR-363.The expression of Mcl-1 and miR-363 was detected by real-time PCR in normal liver cell line LO2 and hepatocellular carcinoma cell line HepG2, Huh7 and PLC. miR-363 was transfected into the HepG2 cells, and then the level of Mcl-1 was measured.The relative viability was evalua-ted by MTT assay after the HepG2 cells were transfected with miR-363, and the apoptosis was analyzed by flow cytometry with Annexin V/PI staining.RESULTS:Bioinformatic analysis identified that there was a putative target site in the Mcl-1 mRNA for miR-363.Transfection of miR-363 mimics suppressed Mcl-1 expression in the HepG2 cells.Transfection of miR-363 mimics inhibited the cell viability as well as inducing cell apoptosis in HepG2 cells.CONCLUSION: Over-ex-pression of miR-363 significantly inhibits the cell viability and induces apoptosis in HepG2 cells, and the mechanism may be related to the downregulation of Mcl-1 caused by miR-363 transfection.