Objective To investigate the efficacy of intensity-modulated radiotherapy (IMRT) in the treatment of undifferentiated nasopharyngeal carcinoma (NPC) and the changes of serum epithelial cadherin (sE-cad) and platelet-derived growth factor (PDGF) levels before and after treatment. Methods A total of 84 patients with NPC (undifferentiated type) admitted to our hospital from June 2019 to June 2021 were selected as the research objects, and divided into the observation group and the control group according to the random number table method according to the ratio of 1:1, with 42 cases in each group. The control group was treated with three-dimensional conformal radiation therapy (3DCRT), and the observation group was treated with IMRT. The curative effect, tumor marker levels [carcinoembryonic antigen (CEA), squamous cell carcinoma-associated antigen (SCC-Ag), keratin 19 fragment 21-1 (CYFRA21-1)], and quality of life core scale were compared between the two groups before and after treatment. (QLQ-C30) score, fibrosis indexes [hyaluronic acid (HA), laminin (LN), procollagen type III (PCIII)], serum sE-cad, PDGF levels and the incidence of complications. Results The disease control rate in the observation group was 85.71% compared with 71.43% in the control group, with no significant difference (P>0.05). After treatment, the serum CEA, SCC-Ag and CYFRA21-1 levels in the observation group were lower than those in the control group (P<0.05). After treatment, the QLQ-C30 score of the observation group was lower than that of the control group (P＜0.05); the serum HA, LN and PCⅢ levels of the observation group after treatment were lower than those of the control group (P＜0.05); The level was lower than that of the control group (P<0.05); the incidence of complications in the observation group was lower than that in the control group (P<0.05). Conclusion Compared with 3DCRT, the effect of IMRT in the treatment of undifferentiated NPC is similar, but it can effectively reduce tumor markers, serum sE-cad and PDGF levels, improve the quality of life, and has less impact on normal tissues with high safety. Keywords: undifferentiated type; three-dimensional conformal radiation therapy; intensity-modulated radiation therapy; tumor markers; nasopharyngeal carcinoma; complications