Epidermal growth factor receptor (EGFR) was expressed widely in NPC. The aim of this study was to investigate the difference of expression of EGFR and Ki67 in primary and recurrence of NPC to supply a micro-evidence of anti-EGFR targeted maintenance therapy for NPC. A retrospective review of 40 patients with clinical stages I-IV b was performed. Chemoradiation was included chemotherapy with fluorouracil plus cisplatin and irradiation for primary and lymph draining regions. All patients were verified tumor locoregional relapse with/or without distant metastasis by CT or MRI after combined CRT by primary and recurrence biopsies. The correlation between EGFR and Ki67 expression inspected by immunohistochemistry was analyzed. The difference of time to recurrence grouped by different expressions of EGFR and Ki67 was compared by log-rank test. The median follow-up time was 20.0 months ± 2.70 (range 23-71). EGFR and Ki67 expression in primary was not significantly different with recurrent focus. A strong significant correlation between EGFR and Ki67 molecules expression was obtained in primary (r = 0.573; P = 0.001) and in recurrent focus (r = 0.698; P = 0.000). A significantly shorter time to locoregional relapse in patients with positive expression of EGFR than patients with negative EGFR expression in primary (P = 0.010) and in relapse (P = 0.022). There was no significant difference of EGFR and Ki67 expression in primary and recurrence tumor expression. The time to relapse was significantly shorter in high expression of EGFR, which might supply micro-evidence to anti-EGFR targeted maintenance therapy for those patients with EGFR overexpression in primary tumor.