<b><i>Background/Aims:</i></b> Endoscopic vidian neurectomy (EVN) for allergic rhinitis (AR) has good clinical effects. However, the pathophysiological basis of the effect of EVN on AR is still poorly understood. This study aimed to investigate the efficacy of EVN on house dust mite (HDM)-sensitive AR and the dynamic changes of serum immunoglobulin E and some immune regulatory factors. <b><i>Methods:</i></b> Twenty HDM-sensitive AR patients were treated with bilateral EVN (EVN group), 15 HDM-sensitive AR patients were treated with subcutaneous immunotherapy (SCIT group), and 15 healthy subjects served as healthy controls. Quality of daily life was assessed by the scores of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs). The visual analog scale was used to assess clinical efficacy. Serum molecules were measured by ELISA and the UNICAP system. <b><i>Results:</i></b> Compared with the SCIT group, the RQLQs in the EVN group were lower 12 months after treatment (both <i>p</i> < 0.05). There was no significant difference in improving nasal itching and sneezing (both <i>p</i> > 0.05), but the clinical efficacy of bilateral EVN was greater than SCIT in improving nasal obstruction, rhinorrhea, eye itching, and lachrymation 12 months after treatment (all <i>p</i> < 0.05). Compared with before treatment, the serum levels of total immunoglobulin E (tIgE), <i>Dermatophagoides pteronyssinus</i>- and <i>Dermatophagoides farinae</i>-specific immunoglobulin E (sIgE), and tumor necrosis factor (TNF)-α in the EVN group and the serum levels of TNF-α and interleukin-4 in the SCIT group were lower 12 months after treatment (all <i>p</i> < 0.05). <b><i>Conclusion:</i></b> The short-term efficacy of bilateral EVN is more effective than SCIT in treating HDM-sensitive AR. This may be because the surgery reduced the tIgE and sIgE levels. TNF-α may be involved in the therapeutic mechanism.