Toll-IL1 receptor (TLR) and TIR signaling pathway genes (IRAK4, MyD88) deficiencies are an inborn error of the innate immune system. Defect in these two genes results in improper downstream signaling of the TLR and TIR pathways which is the important step for the activation of innate and adaptive immune systems. This study aimed to complement the differentially expressed genes (DEGs) innate immune response of patients with inborn errors in Toll-IL1 receptor signaling pathway (IRAK4, MyD88 deficiencies) compared to healthy subjects, identify their functions and molecular pathways. In order to identify key genes, enriched pathways, and important modules in the patients with such inborn innate immune system errors data for gene expression profiles (GSE25742) were downloaded from the GEO database, and bioinformatics analysis was made. In total 500 DEGs were identified. Among them, 191 (38.2%) genes were up-regulated and 309 (61.8%) genes were down-regulated. Gene ontology (GO) and KEGG pathway enrichment analysis of target genes was performed. Furthermore, we reviewed some relevant core genes such as TNF, IL1B, TLR2, MMP9, SPL1, ITAGAX, HCK, Lyn, CXCL1, and FPR2 by using gene-gene interaction network analysis, which may contribute to a better understanding of the molecular mechanisms of the inborn error of innate immunity or TLR signaling. Whereas six clusters were identified by MCODE. These genes and pathways repotted might provide a new perspective for revealing the underlying pathological mechanisms and therapy strategy for inborn error in Tool like receptor signaling pathways and other inborn errors of the innate immune system.