MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by inhibiting translation and decreasing the stability of the targeted transcripts. Over the last two decades, miRNAs have been recognized as important regulators of cancer cell biology, acting either as oncogenes or tumor suppressors. The polycistronic miR-106b∼25 cluster, located within an intron of MCM7 gene, consists of three highly conserved miRNAs: miR-25, miR-93 and miR-106b. A constantly growing body of evidence indicates that these miRNAs are overexpressed in numerous human malignancies and regulate multiple cellular processes associated with cancer development and progression, including: cell proliferation and survival, invasion, metastasis, angiogenesis and immune evasion. Furthermore, recent studies revealed that miR-106b∼25 cluster miRNAs modulate cancer stem cells characteristics and might promote resistance to anticancer therapies. In light of these novel discoveries, miRNAs belonging to the miR-106b∼25 cluster have emerged as key oncogenic drivers as well as potential biomarkers and plausible therapeutic targets in different tumor types. Herein, we comprehensively review novel findings on the roles of miR-106b∼25 cluster in human cancer, and provide a broad insight into the molecular mechanisms underlying its oncogenic properties.