〔Abstract〕 Objective To investigate the mechanism of miR-224-5p on proliferation, apoptosis, invasion and migration of human hepatocellular carcinoma HepG2 cells. Methods The RNA expression levels of miR-224-5p and early growth responsive gene 2(EGR2) in patients with hepatocellular carcinoma were obtained from the TCGA dataset. Normal human hepatocytes LO2 and hepatoma cells HepG2 were cultured in vitro, and the HepG2 cells were transfected with lentiviral vectors(knockdown of miR-224-5p), small interfering RNA fragments or overexpression vectors(interference and overexpression of EGR2). The expression levels of miR-224-5p and EGR2 in hepatocellular carcinoma cDNA chips and cells were detected by quantitative real-time PCR(qPCR). The expression level of EGR2 protein was detected by Western blot. Dual luciferase reporter gene assay was used to detect the binding of miR-224-5p to EGR2. HepG2 cells positive rate were detected by EdU assay, apoptosis rate was detected by flow cytometry, cell invasion number was detected by Transwell assay, and cell mobility was detected by scratch assay. Results Compared with paracancerous tissues, the expression of miR-224-5p was increased and the expression of EGR2 mRNA decreased in HCC tissues. Compared with LO2 group, the expression of miR-224-5p in HepG2 cells increased, and the expression of EGR2 mRNA and protein decreased. Compared with the Lv-sh-NC group, the 24 h EdU positive cell rate, cell invasion number, and 48 h cell mobility of HepG2 cells in the Lv-sh-miR-224-5p group decreased, while the apoptosis rate increased. Compared with Oe-NC group, 24 h EdU positive cell rate, cell invasion number, and 48 h cell mobility of HepG2 cells in Oe-EGR2 group decreased, while apoptosis rate increased. Compared with Lv-sh-NC group, the expression of EGR2 protein in Lv-sh-miR-224-5p group increased. Compared with Lv-sh-miR-224-5p+si-NC group, 24 h EdU positive cell rate, cell invasion rate, and 48 h cell mobility of HepG2 cells in Lv-sh-miR-224-5p+si-EGR2 group increased, while apoptosis number decreased. Conclusion miR-224-5p can promote proliferation, invasion, and migration of HepG2 cells and inhibit apoptosis via binding with EGR2.