Background: To assess clinical application of computed tomography (CT)-guided I-125 seed implantation for patients who cannot endure or unwillingly receive repeated surgery, chemotherapy, or radiotherapy for unmanageable cervical lymph node metastases in head and neck cancer (HNC). Methods: Thirty-one consecutive patients received CT-guided I-125 seed implantation between February 2010 and December 2013. To evaluate the clinical efficiency, karnofsky performance score (KPS), numeric rating scale (NRS), and tumor volume at 3-, and 6-month post-implantation were compared with pre-implantation, along with local control rate (LCR), overall survival rate (OSR), and complications at 3, 6 months, 1, and 2 years. Results: The tumor volume was obviously decreased at 3-, and 6-month post-implantation (21.23 +/- 8.83 versus 9.19 +/- 7.52 cm(2); 21.23 +/- 8.83 versus 6.42 +/- 9.79 cm(2); P < 0.05) compared with pre-implantation. The NRS was statistically reduced (3.06 +/- 1.06 versus 7.77 +/- 0.92; 2.39 +/- 1.15 versus 7.77 +/- 0.92; P < 0.05), while KPS was significantly improved (83.18 +/- 5.97 versus 73.60 +/- 7.90; 82.86 +/- 5.43 versus 73.60 +/- 7.90; P < 0.05) postoperatively at 3 and 6 months, respectively. The LCR at 3, 6 months, 1, and 2 years was 96.30, 83.87, 64.51, and 45.16 %, respectively. The OSR was 100, 100, 67.74, and 45.16 %, respectively. Three cases experienced grade I and two had grade II acute radiation toxicity. Conclusions: CT-guided seed implantation may be feasible and safe for HNC patients whose neck nodes are not manageable by routine strategies with fewer complications, higher LCR, and significant pain relief.