Objective: In this study, we compared the effects of combination of celecoxib, intensity-modulated radiation therapy (IMRT) and hippocampal sparing, IMRT with hippocampal sparing and IMRT only on cognitive function, life quality and therapeutic effects in patients with nasopharyngeal carcinoma (NPC). Methods: From June 2015 to December 2016, 177 cases with NPC in our hospital were finally enrolled and randomly divided into three groups: IMRT only group (I group), hippocampal sparing IMRT (H group) and celecoxib combined with hippocampal sparing IMRT group (Ce group). Cognitive function and life quality were evaluated three months after treatment via Mini-Mental State Examination (MMSE) and Quality of life questionnaire (QLQ C30) respectively. Indicators for therapeutic effects including complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD), adverse reactions, recurrence and metastasis of tumor and serum tumor marker carcinoembryonic antigen (CEA) level of patients were also compared. Results: Before the intervention, there was no difference in cognitive function score among all the patients (P = 0.876). After the treatment, no significant difference was found for RR among groups (P = 0.245), however, patients in the Ce group showed the highest cognitive function score (P < 0.001); the differences in adverse reactions including dry mouth (P = 0.026, Ce vs. H; P = 0.000, Ce vs. I; P = 0.000, H vs. I), oral mucositis (P = 0.060, Ce vs. H; P = 0.008, Ce vs. I; P = 0.396, H vs. I), skin reaction (P = 0.654, Ce vs. H; P = 0.027, Ce vs. I; P = 0.065, H vs. I), irradiation otitis media (P = 0.097, Ce vs. H; P = 0.009, Ce vs. I; P = 0.051, H vs. I) had statistical significance, and their incidence rates in Ce group were lowest. Meanwhile, recurrence and metastasis were less in the Ce group although the differences were insignificant (P = 0.302 and 0.638). The serum level of CEA was notably lower in Ce group (P = 0.031, Ce vs. H; P = 0.020, Ce vs. I; P = 0.512, H vs. I). Life quality scores about cognitive function and role function of H group and Ce group were higher than that of I group while Ce group was the highest (Cognitive function: P = 0.020, Ce vs. H; P = 0.015, Ce vs. I and P = 0.023, H vs. I; role function: P = 0.039, Ce vs. H; P = 0.011, Ce vs. I and P = 0.031, H vs. I). Conclusion: Celecoxib combined with hippocampus sparing IMRT for the treatment of NPC patients could drastically alleviate cognitive dysfunction, improve life quality and reduce the occurrence of adverse events compared with hippocampal sparing IMRT and IMRT only.