Objective To analyze the factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck. Methods A total of 73 patients (61 males, 12 females; age: (59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by 125I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled. The implanted seeds activity was 11.1-29.6 MBq, and the prescription dose was 80.0-145.0 Gy. CT examination was conducted 3 months after 125I seeds implantation. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, short-term efficacy was classified as effective (complete remission (CR), partial remission (PR)) and ineffective (stable disease (SD), progressive disease (PD)). Univariate analysis of factors affecting short-term effect (gender, age, history of radiation therapy, Karnofsky performance status (KPS) scores, pathological type, the longest diameter of tumor, implantation patterns, seeds activity, immediate postoperative dose delivered to 90% gross tumor volume (D90), and with adjuvant chemotherapy post-surgery or not) were conducted. Variables with P<0.2 were enrolled in logistic multivariate regression analysis. In addition, artificial neural network (ANN) was constructed with all influencing factors as independent variables and short-term efficacy as dependent variables. Finally, receiver operating characteristic (ROC) curve analysis was performed for the common influencing factors in logistic regression analysis and ANN analysis. Results There were 34 with effective results and 39 with ineffective results. Logistic regression analysis indicated that the longest diameter of tumor, immediate postoperative D90, with adjuvant chemotherapy post-surgery or not had significant impacts on the short-term efficacy (Wald values: 6.950, 4.804, 4.790, all P<0.05); According to results of ANN analysis, the top 5 in order of importance for short-term efficacy prediction were immediate postoperative D90, the longest diameter of tumor, age, seeds activity and gender. ROC curve analysis indicated that the longest diameter of tumor and immediate postoperative D90 were the best predictors for short-term efficacy, with the threshold of 5.25 cm and 110.05 Gy respectively, and the area under the curve (AUC) was 0.843 and 0.847 respectively (both P<0.001). Conclusions The short-term efficacy of 125I seeds implantation in the recurrence and metastasis of head and neck tumors is mainly related to the longest diameter of tumor and immediate postoperative D90. Patients with the longest diameter of tumor 110.05 Gy can achieve better efficacy. Key words: Head and neck neoplasms; Recurrence; Neoplasm metastasis; Brachytherapy; Iodine radioisotopes; Radiotherapy, image-guided; Tomography, X-ray computed