Objective To retrospectively compare the efficacy and toxicity between intensity?modulated radiotherapy ( IMRT ) combined with chemotherapy plus targeted therapy and IMRT combined with chemotherapy in the treatment of patients with locally advanced nasopharyngeal carcinoma ( NPC) , and to preliminarily evaluate the necessity of adding targeted drugs to standard chemoradiotherapy . Methods Forty?two patients with stage Ⅲ?Ⅳb NPC who received IMRT combined with concurrent ± adjuvant chemotherapy plus targeted molecular therapy from January 2007 to December 2012 were assigned to experiment group,while 168 patients who received IMRT combined with concurrent ±adjuvant chemotherapy within the same period were assigned to control group. The experiment group was paired with the control group at a ratio of 1vs.4.The survival rates were caculated using Kaplan?Meier method and analyzed using log?rank method,other comparison was perfomed by χ2?test. Results The follow?up rate was 100%.The sample size of experiment group and control group were 42 patients and 168 patients. There were no significant differences in the 3?year OS, LRFS, or DMFS rates between the experiment group and the control group (94?3% vs. 87?3%, P=0?647;100?0% vs. 94?6%,P=0?193;92?2% vs. 89?1%, P=0?744).There were also no significant differences in the incidence rates of grade Ⅲ?Ⅳ gastrointestinal reaction or marrow suppression between the two groups ( 7?1%( 3/42 ) vs. 3?6%( 6/168 ) , P=0?388;26?2%( 11/42 ) vs. 17?3%(29/168),P=0?272).However,the experiment group had significantly higher incidence of grade Ⅲ?Ⅳoral mucositis than the control group ( 40?5%( 17/42 ) vs . 14?9%( 25/168 ) , P=0?000 ) . Conclusions The preliminary results indicate that IMRT combined with chemotherapy plus targeted molecular therapy is not able to substantially improve the OS, LRFS, or DMFS rates in patients with locally advanced NPC. Moreover, it may aggravate radiochemotherapy?induced oral mucositis.