In summary, we comprehensively analyzed miRNA–seq, mRNA–seq and single-cell sequencing profiling and established an integrated miRNA–mRNA–PPI network to screen hub genes in sepsis, the potential hub genes TLR5, FCGR1A, ELANE, GNLY, IL2RB and TGFBR3 and miRNAs that are possible posttranscriptional and regulatory factors related to sepsis prognosis were screened out, the findings provide new prospects for exploration of the physiopathologic mechanisms, diagnosis, and treatment of sepsis. The gene discussed is TLR5; the disease is Sepsis.