To assess the predictive value of Ki-67 expression for adjuvant chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).The authors retrospectively evaluated 1374 patients with stage III-IVa nasopharyngeal carcinoma in Sichuan Cancer Hospital from 2013 to 2019, of which 638 patients received induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT), and 736 patients received concurrent chemoradiotherapy (CCRT) alone. Clinical and pathological features of the patients with LA-NPC were retrieved from the hospital records. Follow-up was measured from the first day of therapy to last examination or death. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and Metastasis-free survival (MFS). The ROC curve was carried out to analyze the Ki-67 cut off value related to OS. According to the cut off value of Ki-67, LA-NPC patients was divided into two groups. The efficacy of neoadjuvant chemotherapy was analysis in the two groups respectively. The OS, PFS, LRFS and MFS rates were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS, PFS, MFS and LRFS.The median (interquartile range) follow-up time was (42.3 months [10.3-62.4]). The level of Ki-67 expression was not significantly correlated with age, gender, T stage, N stage, or histological type. The ROC curve showed that the Ki-67 cut off value related to OS was 50%. Among the LA-NPC patients with higher Ki-67 expression (>50%), we observed a significant difference between IC+CCRT group and CCRT group, including 3-years OS (96.7% vs 75.5%, P = 0.011), PFS (81.7% vs 66.7%, P = 0.007), LRFS (88.9% vs 94.1%, P = 0.530), and MFS (91.9% vs 66.7%, P = 0.003). However, among the LA-NPC patients with lower Ki-67 expression (≤50%), there was no significant difference between IC+CCRT group and CCRT group, including 3-years OS (91.1% vs 80.4%, P = 0.631), PFS (80.9% vs 85.2%, P = 0.921), LRFS (91.6% vs 96.7%, P = 0.312), and MFS (84.0% vs 85.2%, P = 0.913).We found that LA-NPC patients got survival benefit from neoadjuvant chemotherapy may depend on the expression of Ki-67. LA-NPC patients with higher expression of Ki-67 (> 50%) can have a better survival outcome after neoadjuvant chemotherapy. The expression level of Ki-67 was a potential marker for predicting the efficacy of neoadjuvant chemotherapy in LA-NPC.Copyright © 2021. Published by Elsevier Inc.