Cancer is one of the deadliest pathologies with more than 19 million new cases and 10 million cancer-related deaths across the globe. Despite development of advanced therapeutic interventions, cancer remains as a fatal pathology due to lack of early prognostic biomarkers,therapy resistanceand requires identification of novel drug targets. Runt-related transcription factors (Runx) familycontrols several cellular and physiological functions includingosteogenesis. Recent literatures from PubMed was mined and the review was written in comprehensive manner RESULTS: Recent literature suggests that aberrant expression of Runx contributes to tumorigenesis of many organs. Conversely, cell- and tissue-specific tumor suppressor roles of Runx are also reported. In this review, we have provided the structural/functional properties of Runx isoforms and its regulation in context of human cancer. Moreover, in an urgent need to discover novel therapeutic interventions against cancer, we comprehensively discussed the reported oncogenic and tumor suppressive roles of Runx isoforms in several tumor types and discussed the discrepancies that may have risen on Runx as a driver of malignant transformation. Runx may be a novel therapeutic target against a battery of deadly human cancers.