Simple SummaryThe transcription factor RUNX family plays a crucial role in the formation of osteoblasts from bone marrow mesenchymal stem cells, contributing to bone development. However, emerging evidence suggests its involvement in tumor biology and cancer progression. In particular, the RUNX family has been associated with osteosarcoma by regulating factors related to tumorigenicity. As a vital molecule within the regulatory network of cancers, RUNX influences various upstream signaling pathways and downstream target molecules. Understanding the precise mechanisms underlying the development and prognosis of malignant tumors is essential. RUNX has been recognized as a potential therapeutic target for bone cancer, and further research into its role may lead to the development of new medications and improved clinical outcomes.AbstractThe transcription factor runt-related protein (RUNX) family is the major transcription factor responsible for the formation of osteoblasts from bone marrow mesenchymal stem cells, which are involved in bone formation. Accumulating evidence implicates the RUNX family for its role in tumor biology and cancer progression. The RUNX family has been linked to osteosarcoma via its regulation of many tumorigenicity-related factors. In the regulatory network of cancers, with numerous upstream signaling pathways and its potential target molecules downstream, RUNX is a vital molecule. Hence, a pressing need exists to understand the precise process underpinning the occurrence and prognosis of several malignant tumors. Until recently, RUNX has been regarded as one of the therapeutic targets for bone cancer. Therefore, in this review, we have provided insights into various molecular mechanisms behind the tumorigenic role of RUNX in various important cancers. RUNX is anticipated to grow into a novel therapeutic target with the in-depth study of RUNX family-related regulatory processes, aid in the creation of new medications, and enhance clinical efficacy.