Abstract: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb) which is a big public health threat. The pathogen-related molecular patterns (PAMPs) of Mtb is recognized by pattern recognition receptors (PRRs) expressed on innate immune cells including macrophages and dendritic cells (DC) and induces the production of specific cytokines and activation of those cells. The activated macrophages and DC are not only able to directly phagocytose Mtb or Mtb infected cells, but also activate adaptive immune responses by releasing active mo-lecules and antigen presentation. However multiple immune evasion strategies have been developed during the co-evolution of Mtb and host immune systems, including inhibiting the production of cytokines, the fusion of phagosome with lysosome, autophagy of macrophages, apoptosis of immune cells as well as maturation and antigen presentation of dendritic cells, which ensure the persistent survival of Mtb in macrophages. Currently, BCG is the solely available TB vaccine however is not very effective. Novel and high effective vaccine development is impeded by the lack of understanding on the pathogenesis of TB. Although many progresses in the development of novel vaccine have been made and more than ten candidate vaccines have stepped into clinical stage, yet there is still a long way to go to fulfill clinical application. Novel vaccines are divided into recombinant BCG vaccine, subunit vaccine, live vector vaccine and attenuated Mtb vaccine according to immune strategies and improvement methods. There are several key problems to develop novel vaccines. Firstly, good antigens have to be obtained. Secondly, excellent adjuvant has to be acquired so as to enhance the protective effect of antigen. Thirdly, the processing and presentation of antigens should be ensured correctly and effectively. Fourthly, the immune memory of BCG vaccination should be enhanced. Fifthly, the toxicity of BCG vaccination should be reduced. Lastly, a simple and reliable vaccine evaluation platform should be set up.