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Objective: To measure setup error of head and neck neoplasm in radiotherapy and discuss over effects of error on physical dose acting on target region and organs at risk of nasopharynx cancer (NPC) patients treated with intensity modulated radiation therapy (IMRT). Methods: A total of 152 patients who developed head and neck neoplasm and received IMRT were randomly selected. Through comparing digital portal image and digital reconstruction image, we measured setup error, calculated expanding margin from clinical target volume (CTV) to planning target volume (PTV) and analyzed whether there was rules between setup error and treatment time. Additionally, 20 cases of NPC were selected. Three-dimensional error was simulated in planning system. Dose distribution was recalculated and a series of dose parameters of target volume and OAR were analyzed. Results: Setup error in left-right, head-feet and ventral-dorsal direction was (-0.62±1.46) mm, (-0.41±1.54) mm and (-0.31±1.67) mm respectively. Regarding limit value, the maximum and minimum value in left-right direction, head-feet direction and ventral-dorsal direction was 2.70 mm and -6.00 mm; 3.00 mm and -5.00 mm, 5.00 mm and -7.50 mm. Expanding margin from CTV to PTV was 2.26 mm, 1.88 mm and 1.97 mm in left-right direction, head-feet direction and ventral-dorsal direction. Conclusion: During IMRT, only when setup error is controlled below 3 mm can sharply reduce the damage caused by radiation to normal tissue; therefore, quality security and control of electronic portal imaging device need (EPID) to be improved.