Aim To explore whether hydrogen sulfide （H₂S） protects H9c2 cells against doxorubicin-induced injury by modulating p38 mitogen-activated protein kinase（MAPK） pathway. Methods H9c2 cells were treated with doxorubicin（DOX） to establish the model of cardiac cell injury In order to explore the protective effect of H₂S, cells were pretreated with 400 μmol/L NaHS （a donor of H₂S）for 30 min before exposure to DOX. The expression level of p38MAPK protein was tested by Western blot Cell viability was measured by cell counter kit-8 （CCK-8） Morphological changes of apoptotic cells were detected by Hoechst 33258 staining Intracellular level of reactive oxygen species （ROS） was measured by DCFH-DA staining and photofluorography. Results At range of 15 to 60 min, DOX at 5 μmol/L time-dependently upregulated expression level of phosphorylated（p） p38MAPK. Pretreatment with 400 μmol/L NaHS for 30 min before exposure of H9c2 cells to DOX not only obviously inhibited upregulation of p-p38MAPK expression induced by DOX, but also significantly blocked DOX-induced cardiomyocyte injuries, as evidenced by an increase in cell viability, decreases in amount of apoptotic cells and intracellular ROS generation. Similar to the cardioprotective effect of NaHS, pretreatment with SB203580 （an inhibitor of p38MAPK） for 60 min also protected H9c2 cardiac cells against DOX-induced injury. Conclusion p38MAPK pathway participates in DOX-induced cardiomyocyte damage H₂S may protect cardiomyocyte against DOX-induced injury by inhibiting p38MAPK pathway.