Hypoxia may cause diseases in human beings. The up- or down- regulation of lncRNAs were identified to possess the ability to protect the myocardial cells from hypoxia injury. This study explored the role of lncRNA GAS5 in sodium Hydrosulfite Induced Hl-1 Cells in vitro. RT-qPCR was applied to measure the expressions of RNAs whereas the cell viability was detected with CCK-8. Luciferase report assay was performed to validate the binding between lncRNA GAS5 and miR-222-3p. The proteins regarding PI3K/AKT signaling were evaluated through western blot analysis. The results showed that the hypoxia could reduce cell viabilities and enhance the apoptosis. Meanwhile, the PI3K/AKT signaling pathway was suppressed as well. lncRNA GAS5 got expressed higher in hypoxic cells whereas the suppressed GAS5 was able to increase cell viabilities while inhibiting apoptosis. MiR-222-3p was the target gene of lncRNA as determined by the luciferase report assay and its expressions were low in hypoxic cells. The overexpressed miR-222-3p could promote proliferation and inhibit apoptosis. Then, the correlation of GAS5 and miR-222-3p was measured which showed that miR-222-3p could resume the functions of GAS5 in cell viabilities and apoptosis through protein regulation in PI3K and AKT signaling pathways. Copyright © 2020. Published by Elsevier Inc.