Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns. It is of critical importance for clearing invading pathogens and controlling bacterial infections through modulating inflammation. However, excessive host inflammatory responses may trigger organ failure, disrupt tissue homeostasis and induce immune disorders. Emerging evidence has shown that Notch signaling interacts with components of TLRs and participates in regulating immune responses. In this review, we discussed how Notch pathways interact with TLRs pathway and how these two pathways coordinate to regulate immune response, particularly polarization of macrophages, differentiation of dendritic cells, activation of T cell subsets.