Abstract: Most carcinogenic mutations, including those causing a loss of function, are not directly "druggable" with traditional small-molecule inhibitors, such as targeted drugs. Thus, despite our growing cognition of carcinogenic mutations that drive tumor progression, there are still problems regarding targeted therapy for tumors. The application of synthetic lethality effects is expected to become a new breakthrough in tumor-targeted therapy. Therefore, identifying a combination of genetic mutations that generate synthetic lethality effects plays important roles in targeted therapy for tumors. This article reviews the origin and development of synthetic lethality effects, the forms of interaction, related screening techniques, clinical treatment strategies, and significance and challenges.