microRNAs (miRNAs) are an abundant class of small non-coding RNAs that function as gene regulators. Although deregulation of miRNA expression is involved in the initiation and progression of tumorigenesis, the underlying mechanisms of miRNA deregulation in human cancer are still largely unknown. Increasing evidence indicates that transcriptional deregulations, epigenetic alterations, mutations, DNA copy number abnormalities and defects in the miRNA biogenesis machinery might contribute to miRNA deregulation in human cancer. A clearer understanding of the mechanisms involved in miRNA deregulation in human cancer will contribute greatly to the development of new miRNA-based strategies in cancer diagnosis and treatment.