ObjectiveTo construct a survival prediction model for patients with TNM stage III hepatocellular carcinoma (HCC) to guide the clinical diagnosis and treatment of HCC patients and improve prognosis.MethodsBased on data from patients with stage III (AJCC 7th TNM stage) recorded by the American Institute of Cancer Research from 2010 to 2013, risk factors affecting the prognosis were screened by Cox univariate and multivariate regression, line plots was constructed, and the credibility of the model was verified by Boostrap method. ROC operating curves, calibration curves and DCA clinical decision curves were used to evaluate the model, and Kaplan–Meier was used for survival analysis was used to evaluate the efficacy of the model. External survival data from patients newly diagnosed with stage III hepatocellular carcinoma during 2014–2015 were used to validate and fit the model and to optimize the model.ResultsAge > 75 years vs.18-53 years [HR = 1.502; 95%CI(1.134–1.990)], stage IIIC vs. Stage IIIA [HR = 1.930; 95%CI(1.509–2.470)], lobotomy vs. non-surgery [HR = 0.295; 95%CI(0.228–0.383)], radiotherapy vs. non-radiotherapy [HR = 0.481; 95%CI(0.373–0.619)], chemotherapy vs. Non-chemotherapy [HR = 0.443; 95%CI(0.381–0.515)], positive serum AFP before treatment vs. negative [HR = 1.667; 95%CI(1.356–2.049)], the above indicators are independent prognostic factors for patients with stage III hepatocellular carcinoma, and thePvalues for the above results were less than 0.05. A joint prediction model was constructed based on age, TNM stage, whether and how to operate, whether to receive radiotherapy, whether to receive chemotherapy, pre-treatment serum AFP status and liver fibrosis score. The consistency index of the improved prognosis model was 0.725.ConclusionsThe traditional TNM staging has limitations for clinical diagnosis and treatment, while the Nomogram model modified by TNM staging has good predictive efficacy and clinical significance.