Objective To establish a predictive model for long-term tumor-specific survival after surgery for patients with intermediate to advanced medullary thyroid cancer (MTC) based on American Joint Committee on Cancer (AJCC) TNM staging, by using the Surveillance, Epidemiology, and End Results (SEER) Database. Methods The data of 692 patients with intermediate to advanced MTC who underwent total thyroidectomy and cervical lymph node dissection registered in the SEER database during 2004–2017 were extracted and screened, and were randomly divided into 484 cases in the modeling group and 208 cases in the validation group according to 7∶3. Cox proportional hazard regression was used to screen predictors of tumor-specific survival after surgery for intermediate to advanced stage MTC and to develop a Nomogram model. The accuracy and usefulness of the model were tested by using the consistency index (C-index), calibration curve, time-dependent ROC curve and decision curve analysis (DSA). Results In the modeling group, the multivariate Cox proportional hazard regression model indicated that the factors affecting tumor-specific survival after surgery in patients with intermediate to advanced MTC were AJCC TNM staging, age, lymph node ratio (LNR), and tumor diameter, and the Nomogram model was developed based on these results. The modeling group had a C-index of 0.827 and its area under the 5-year and 10-year time-dependent ROC curves were 0.865 [95%CI (0.817, 0.913)], 0.845 [95%CI (0.787, 0.904)], respectively, and the validation group had a C-index of 0.866 and its area under the 5-year and 10-year time-dependent ROC curves were 0.866 [95%CI (0.798, 0.935)] and 0.923 [95%CI (0.863, 0.983)], respectively. Good agreement between the model-predicted 5- and 10-year tumor-specific survival rates and the actual 5- and 10-year tumor-specific survival rates were showed in both the modeling and validation groups. Based on the DCA curve, the new model based on AJCC TNM staging was developed with a significant advantage over the former model containing only AJCC TNM staging in terms of net benefits obtained by patients at 5 years and 10 years after surgery. Conclusion The prognostic model based on AJCC TNM staging for predicting tumor-specific survival after surgery for intermediate to advanced MTC established in this study has good predictive effect and practicality, which can help guide personalized, precise and comprehensive treatment decisions and can be used in clinical practice.