Mycobacterium tuberculosis ( Mtb) is an extremely successful intracellular bacterial pathogen that engages multiple strategies to escape host immune surveillance,so as to survive within host macrophages for long period. Upon the invasion of pathogenic bacteria,the host ubiquitin system plays a critical role in activating the host innate immune responses and associated signaling pathways such as inflammatory and immune responses, autophagy, phagosome maturation and cell death, etc. On the other hand, recent studies have demonstrated that intracellular pathogenic bacteria such as Mtb can secrete a variety of effector proteins into host cells to hijack or co-opt the ubiquitin system to suppress host immune responses. Those pathogen-host interacting interfaces could provide potential novel targets for the development of anti-tuberculosis drugs.