Objective To investigate the relationship of the expressions of Kruppel-like factor 5 (KLF5) and Kruppel-like factor 9 (KLF9) with the recurrence of nasopharyngeal carcinoma (NPC) in the elderly patients. Methods A retrospective analysis was made of the clinical data of 263 elderly NPC patients admitted to Hunan Provincial Brain Hospital from May 2016 to May 2018. All patients were followed up for 5 years after treatment to observe for recurrence. Protein expression levels of KLF5 and KLF9 in the cancer tissues of the patients were detected using Western blotting technique. The recurrent and non-recurrent patients were compared for the basic data [gender, age, union for international cancer control (UICC) stage, pathological type, duration of extended treatment, radiotherapy dose, radiotherapy combined with chemotherapy, nasal invasion, oropharyngeal invasion, skull base bone invasion, intracranial damage, cranial nerve injury] and KLF5 and KLF9. Multivariate logistic regression was used to analyze the risk factors of recurrence in the elderly NPC patients . SPSS 22.0 was used for statistical analysis. Comparison between two groups was performed using t test or χ² test depending on the data type. Results A total of 263 elderly NPC patients were followed up for 5 years after treatment, and 27 (10.27%) experienced relapse. Compared with the non-recurrent patients, the recurrent patients had higher proportions of those with UICC stage Ⅲ to Ⅳ, those without radiotherapy combined with chemotherapy, those with skull base bone invasion, and those with cranial nerve injury, and the differences were statistically significant (all P<0.05). Compared with non-relapse patients, the expression of KLF5 and KLF9 in the relapse patients decreased, and the differences were statistically significant (P<0.05). Receiver operating characteristic (ROC) curve analysis of KLF5 and KLF9 showed better predictive value for the NPC recurrence in the elderly patients, and the combined predictive value was higher, and the area under the curve (AUC) was 0.800,0.790 and 0.894, respectively (P<0.05). Multivariate logistic regression analysis showed that UICC stage Ⅲ-Ⅳ (OR=3.420,95%CI 1.715-6.820), no radiotherapy combined with chemotherapy (OR=1.434,95%CI 1.106-1.859), skull base bone invasion (OR=2.790,95%CI 1.337-5.822), cranial nerve injury (OR=1.249,95%CI 1.026-1.520), KLF5 < 2.495 (OR=4.453,95%CI 1.469-13.498), KLF9＜0.305 (OR=2.719,95%CI 1.604-4.609) were risk factors for NPC recurrence in the elderly patients. Conclusion The expressions of KLF5 and KLF9 in the cancer tissues of the elderly NPC patients decrease and are factors affecting the recurrence.