Osteosarcoma (OS) is one of the most prevalent and highly aggressive bone malignancies. The treatment strategies of OS is under standard regimens, including surgical resection, chemotherapy, and other adjuvant therapy. However, the 5-year survival rate is still unsatisfactory. Previous studies have demonstrated that the expression of miR-34a decreases in osteosarcoma, which is involved in regulating numerous genes directly or indirectly at the post-transcriptional level and other pathways. Thus, miR-34a plays an important role in mediating OS cell proliferation, differentiation, migration, and apoptosis, and might be a pivotal biomarker for OS with diagnostic and therapeutic potentials. In this review, we aim to summarize the relationship between miR-34a and OS, with an emphasis on the specific mechanisms in OS development referring to miR-34a. Moreover, the potential role of miR-34a as a diagnostic, prognostic, and therapeutic candidate for OS would be presented in detail. However, the molecular mechanisms related to miR-34a and OS remain elusive, and more investigations are needed to reach a comprehensive understanding.