Tuberculosis has brought serious disease burden to the world, prevention and control of tuberculosis is of great significance. Molecular epidemiology of tuberculosis integrates the technique of Mycobacterium tuberculosis typing and epidemiological data, and plays an extremely important role in the study of the spread and epidemic characteristics of tuberculosis. Whole genome sequencing (WGS) can construct complete DNA sequences of the genome of an organism, which has the advantages of high resolution, high throughput and accurate results, it is very attractive and has great development potential in the study of molecular epidemiology of tuberculosis. This paper compares WGS technique with the traditional Mycobacterium tuberculosis typing technique, points advantages of WGS, introduces technical route and progress of WGS, reviews its application achievements in epidemic tracing, drug resistance research and mixed infection diagnosis, so as to provide reference and support for prevention, control and research of tuberculosis.