To conclude, our findings revealed that miR-539-5p was significantly down-regulated in LPS-induced H9c2 cells, and up-regulation of miR-539-5p ameliorated inflammation response, viability, proliferation, and apoptosis of LPS-induced H9c2 cells via targeting IRAK3, indicating that miR-539-5p might be a potential new target for the treatment of LPS-induced sepsis. Here, IRAK3 is linked to Sepsis.