Healthcare-associated infection outbreaks are a serious threat to patient safety and often cause serious consequences. The use of genotyping methods to identify the source of infection and the route of transmission in outbreaks is a critical point in controlling outbreaks. Recently, the use of whole-genome sequencing (WGS) makes it faster and much more accurate. Compared with traditional methods, WGS can distinguish highly correlated pathogen lineages, track infection source accurately and help researchers understanding the propagation dynamics model, and even provide more target intervention information. The application of WGS technology in healthcare-associated infection outbreak investigation and control is reviewed in this paper, and its advantages and challenges are also evaluated.