The present study is to compare the efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) combined with endostar and IMRT combined with concurrent chemotherapy on locally advanced nasopharyngeal carcinoma (NPC).A total of 23 patients with stage III-IVa NPC were included in the present study, and randomly divided into experimental group (10 cases treated with IMRT + endostar) and control group (13 cases treated with IMRT + chemotherapy of cis-dichlorodiamineplatinum). Endostar was intravenously administered from the first day of IMRT. The patients received a total of 2 cycles (14 days each) separating by a 7-day interval.IMRT combined with endostar did not have significantly different recent efficacy compared with IMRT combined with chemotherapy. IMRT combined with endostar and IMRT combined with chemotherapy had 2-year overall survival (OS) rates of 100.0% and 69.6%, respectively, without significant difference between each other (χ = 1.446, P = .299). The 2-year local relapse-free survival (LRFS) of the 2 groups were 100.0% and 81.3%, respectively, without significant difference between each other (χ = 1.000, P = .317). The 2-year distant metastasis-free survival (DMFS) of the 2 groups were 100.0% and 73.5% (χ = 1.591, P = .207), respectively. The 2-year progression-free survival (PFS) of the 2 groups were 100.0% and 67.3% (χ = 2.164, P = .141), respectively. However, the cumulative survival curves of OS, LRFS, DMFS, and PFS were separated between the 2 groups. The result that IMRT combined with endostar did not have significantly different long-term efficacy than IMRT combined with chemotherapy probably due to limited case number and short follow-up time. IMRT combined with endostar resulted in significantly lower grades of leucopenia, nausea/vomiting, weight loss, and oral mucositis compared with IMRT combined with chemotherapy. The grades of late adverse reactions of IMRT combined with endostar were not different from those of IMRT combined with chemotherapy.The present study demonstrates that, compared with IMRT combined with chemotherapy, IMRT combined with endostar has similar efficacy in the treatment of locally advanced NPC, but significantly weaker acute adverse reactions, which improve the life quality of NPC patients.