In our report, the acknowledged public datasets and machine learning were used to determine the role of apoptosis in sepsis and identify 11 DEGs including: CASP8, VDAC2, CHMP1A, CHMP5, FASLG, IFNAR1, JAK1, JAK3, STAT4, IRF9 and BCL2. Further, 4 hub genes (BCL2, FASLG, JAK3 and IFR9) were emerged as remarkable diagnostic signatures, which was supported by validation of external datasets. Here, CASP8 is linked to Sepsis.