〔Abstract〕 Objective To investigate whether NaHS, a hydrogen sulfide donor, can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc-/GPX4 signaling pathway in ferroptosis. Methods Lipopolysacc-haride( LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sepsis,which was divided into Control group,LPS group and LPS + Na HS group. The kits were applied to detect the changes of cardiomyocyte viability,Fe2 +,LDH and CK-MB,determine the levels of oxidative stress indexes GSH and MDA,detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes,and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results Compared with the Control group,H9c2 cell viability decreased,Fe(2 +) concentration increased,GSH,MDA and ROS levels increased,mitochondrial JC-1 monomer increased,expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased,and cell damage increased after LPS stimulation( P<0. 05). Compared with the LPS group,Na HS attenuated LPS-induced H9c2 cell injury and elevated Fe2+concentration,decreased the level of LPS-induced oxidative stress in H9c2 cells,and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4( P<0. 05). Conclusion The mechanism by which Na HS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc-/GPX4 signaling pathway in ferroptosis.