To study the effect and mechanism of luteolin (Lut) on H9c2 myocardial cell injury.The rat H9c2 myocardial cell line was used to establish a myocardial cell injury model with 1 μM doxorubicin (Dox).Different concentrations of Lut (5,10,20 μM) were used for intervention.Cell viability was measured by MTT assay.High-throughput transcriptome sequencing was used to screen the target genes of Lut (20 μM) for improving H9c2 myocardial cell injury.The extend myocardial cell mitochondria Factor 1 (mitochondrial elongation factor 1,MIEF1) expression was suppressed by use molecular cloning technology.Western blot was performed to detect the expression levels of MIEF1,phosphorylated-Drp1 (p-Drp1,Ser637),and Caspase-3 in myocytes with low MIEF1 expression by Lut.Compared with Dox group,Lut significantly improved the cell viability of H9c2 (P < 0.05).3 582 differentially expressed genes were found in Dox group compared with the normal group.1 981 differentially expressed genes were obtained in Lut plus Dox group compared with Dox group.Small interfering RNA (siRNA) was used to interfere with the construction of MIEF1 low expression cardiomyocytes.Western blot results showed that,Lut increased the expression level of MIEF1 and p-Drp1(Ser637) protein in myocytes with low expression of MIEF1 (P < 0.05) and decreased the expression level of Caspase-3 (P < 0.05).In conclusion,the protective effect of Lut on H9c2 cardiomyocytes may be related to the promotion of MIEF1 expression,the results of this experiment provide a theoretical basis for the treatment of doxorubicin induced cardiomyocyte injury.