Curcumin (Cur) has been reported to function as an antioxidant and anti‑inflammatory agent and to play a role in anti‑atherosclerosis. The present study aimed to explore the protective effect of Cur on hypoxia/reoxygenation (H/R) injury. The morphological changes in H9c2 cardiomyocytes were observed under an inverted microscope. Cell viability was determined by Cell Counting Kit‑8 (CCK‑8). Lactate dehydrogenase (LDH) level, malondialdehyde (MDA) level and the antioxidant superoxide dismutase (SOD) activity were determined by corresponding kits. Apoptosis and reactive oxygen species (ROS) levels were determined by flow cytometry. Endoplasmic reticulum (ER) stress‑related factors, which were examined by quantitative real‑time polymerase chain reaction (qPCR) and western blot analysis, included 78‑kDa glucose‑regulated protein (GRP78) and C/EBP homologous protein (CHOP). Extracellular signal regulating kinase 1/2 (ERK1/2), p38, c‑Jun NH2‑terminal kinase (JNK) and the phosphorylation levels of key proteins in the mitogen‑activated protein kinase (MAPK) signaling pathway were all determined by western blot analysis. Compared to the control group, the cell morphology of the H9c2 cells was obviously altered upon H/R. Cell viability was significantly decreased, while apoptosis was significantly increased by H/R. We also observed that the levels of LDH and MDA were elevated and the activity of SOD was decreased in the H/R group. Notably, LDH, MDA and SOD levels were reversed following treatment with Cur; while apoptosis and ROS levels in the H/R injury group were decreased by Cur. H/R injury‑triggered ER stress and the MAPK signaling pathway were suppressed by Cur. These results demonstrated that Cur has a protective effect on cardiomyocytes via suppression of ER stress and the MAPK pathway.