PurposeThis study assessed the therapeutic efficacy of postoperative magnetic resonance (MR)‐guided interstitial 125I seed implantation for treatment of oral and maxillofacial malignant tumors.Methods and MaterialsA total of 127 patients with oral or maxillofacial malignant tumors were included in this study who received interstitial 125I treatment after the surgery resection. Before implantation, all the patients received MR scans to assess the lesion scope, extent, and nature. 125I implantation target regions were based on the pre‐operative imaging. 125I seeds were delivered to target regions via puncture needles under the real‐time guidance of MR. Computed tomography (CT)or MR was performed immediately after implantation and again every 3 months later.ResultsAfter successful 125I implantation, all patients were also examined regularly to detect tumor recurrence, lymphatic, and distant metastases. To date, CT or MR verification showed that 13/127 patients experienced tumor recurrence or lymphatic metastasis or distant metastasis. No seeds migration was observed, no serious treatment‐related complications affected patient quality of life, and no important organ (such as major cervical vessels, spinal cord, etc.) injuries were observed.ConclusionOur results show that MR‐guided 125I implantation is an effective approach to site‐specific treatment for oral and maxillofacial tumor, which could potentially reduce postoperative complications and tumor recurrence rates, increase patient survival, and improve quality of life.