〔Abstract〕 Objective To investigate the effect and mechanism of long non-coding RNA RMRP (LncRNA RMRP) on oxygen-glucose deprivation/reperfusion (OGD/R) -induced ferroptosis in mouse HL-1 cardiomyocytes by regula- ting miR-766-5p. Methods HL-1 cells were cultured in vitro , and OGD/R models were established. The expres- sion levels of LncRNA RMRP in HL-1 cells at various reperfusion time points were subsequently quantified using qRT-PCR. The LncRNA RMRP small RNA interference fragment (si-RMRP) and its corresponding negative con- trol (si-NC) , as well as the miR-766-5p inhibitor and its respective negative control (inhibitor-NC) , were trans- fected into HL-1 cells. Subsequently , the cells were subjected to OGD/R treatment. CCK-8 assay was employed to evaluate cell viability. Assay kits were employed to measure the levels of lactate dehydrogenase (LDH) in the cell supernatant , as well as the intracellular levels of malondialdehyde (MDA) , superoxide dismutase (SOD) , gluta- thione (GSH) , and ferrous ion (Fe2 + ) . qRT-PCR analysis was conducted to assess the expression levels of Ln- cRNA RMRP and miR-766-5p. Western blot analysis was conducted to assess the expression levels of proteins asso- ciated with ferroptosis including GPX4 , SLC7A11 , and FTH1 . Dual-luciferase reporter assays were performed to investigate the sponge adsorption relationship between LncRNA RMRP and miR-766-5p. Results As reperfusion time extended , the expression level of LncRNA RMRP in cells progressively increased (P < 0. 01) . Treatment with OGD/R significantly inhibited the viability of HL-1 cells , reduced the expression of miR-766-5p (P < 0. 01) , ele- vated the levels of LDH in the supernatant , as well as MDA and Fe2 + levels within the cells , and decreased the ac- tivities of SOD and GSH in cells (P < 0. 01) . Additionally , OGD/R treatment downregulated the protein expres- sion levels of GPX4 , SLC7A11 , and FTH1(P < 0. 01) . Silencing LncRNA RMRP reversed these effects by enhan- cing the viability of HL-1 cells , increasing miR-766-5p expression (P < 0. 01) , reducing LDH in the supernatant , as well as MDA and Fe2 + levels within the cells , and promoting SOD and GSH activities in cells (P < 0. 01) . Fur- thermore , silencing LncRNA RMRP upregulated the protein expression levels of GPX4 , SLC7A11 , and FTH1(P < 0. 01) . The dual-luciferase reporter assay confirmed that LncRNA RMRP could regulate the expression of miR-766- 5p through a sponge adsorption mechanism. Partial inhibition of miR-766-5p inhibitor expression could mitigate the improvement effect caused by LncRNA RMRP silencing on OGD/R-induced ferroptosis in HL-1 cells. Conclusion Silencing LncRNA RMRP inhibits OGD/R-induced ferroptosis in HL-1 cells , potentially through the sponge-me- diated regulation of miR-766-5p expression.