Several microRNAs, most representing the miR-34, are highly related to tumor suppression protein p53. p53 exerts its tumor suppression function known as inhibiting multiple-oncogenes, such as Bcl-2, c-myc and cell cytokines such as cyclinE2, cyclinD1 and c-Met through the regulation of miR-34. On the other hand, miR-34 enhances the activities of p53 by inhibiting silence information regulator I (SIRTI). The positive feedback regulatory network based on p53 and miR-34 families play an important role in suppression of oncogenesis and deterioration. This paper summarizes the latest advances of p53 highly related miR-34 families in oncogenesis and treatment.