Objective To investigate the clinical features, effective treatment, survival and prognostic factors of second primary tongue squamous cell carcinoma (SPTSCC) after nasopharyngeal carcinoma (NPC) radiotherapy. Methods The clinical data of 35 cases with SPTSCC after NPC radiotherapy were analyzed retrospectively. Kaplan-Meier method, Log-Rank test and COX proportional hazard mode was performed for statistical analysis. Results 3-year and 5-year overall survival rates were 55 % and 47 %, respectively, lymph node metastasis rate was 5.71 %. Univariate analysis indicated that gender (χ2 = 8.89, P = 0.00), T classification (χ2= 5.58, P= 0.02), clinical stage (χ2 = 8.51, P= 0.04) and treatment methods (χ2 = 29.37, P = 0.00) were important factors of prognosis. Multivariate analysis showed that treatment methods (P = 0.00) and T classification (P = 0.03) were independent prognostic factors. Operative treatment group had better prognosis than the non-operative treatment group, the difference was statistically significant (P <0.05), male patients in the risk of SPTSCC was higher than the female patients, and the incidence of SPTSCC was increased along with extension of the time after NPC radiotherapy. Conclusion The rate of the lymph node metastasis is lower for SPTSCC after NPC radiotherapy and treatment patterns and T stage are independent prognostic factors. Long-term follow-up after NPC radiotherapy is necessary to the early diagnosis of SPTSCC, so that to give surgery or combined therapy with surgery in order to achieve a good effect.