Mitogen-activated protein kinase (MAPK) signaling pathway is one of the most important intracellular signaling pathways in which cells perceive exogenous stimuli and make an effective immune response. Recent studies have shown that the dysregulation of MAPK is highly associated with tuberculosis pathogenesis. The MAPK phosphatases (MKPs) are the prototypic phosphatase that could dephosphorylate the MAPKs, thus play an essential role in the regulation of cell stress, differentiation, proliferation and apoptosis by negatively regulating the activity of MAPKs. Among all the MKPs, MKP-1 has the strongest ability to dephosphorylate MAPKs. In this review, we summarize the role of MKP-1 in Mycobacterium tuberculosis infection and relevant research progress.