The ability of the classic tumour-suppressive let-7 family to inhibit carcinogenesis, tumour progression, recurrence and pluripotency of cancer stem cells has generated significant interest in the field of cancer research. Through suppressing and degrading downstream-targeted mRNAs, let-7 affected most aspects of cell biology. It is perplexing how let-7 affects oncogenesis, as the large influx of new miRNAs and other kinds of non-coding RNAs are continuously defined. In this review, we delineate the complex functions of let-7 and discuss the future direction of let-7 research.