Small non-coding microRNAs (miRNAs) regulate gene expression at the post-transcriptional and translational levels. The dysregulated miRNAs are involved in a large variety of diseases including cancer and cardiovascular diseases. MiR-34a is one of the most anti-oncomiRs that is down-regulated in multiple types of cancer. It regulates a wide range of genes and pathways involved in cancer initiation, progression and metastasis. Next to cancer, miR-34a is recently found to be implicated in cardiovascular disease as one damager factor. In this review, we highlight the complex roles of miR-34a in cancer and cardiovascular disease, as well as the therapeutic potentials.