Objective To compare the efficacy of subcutaneous immunotherapy (SCIT) and its impact on quality of life between children with dust mite-allergic asthma who are monosensitized and those who are polysensitized. Methods This prospective longitudinal cohort study enrolled 80 children with dust mite-allergic asthma, who were divided into a monosensitization group (n=40) and a polysensitization group (n=40). All children completed 3 years of standardized dust mite SCIT. Indicators compared between the two groups before and after treatment included peripheral blood eosinophil percentage, fractional exhaled nitric oxide, pulmonary function parameters, visual analog scale score, Asthma Control Test score, quality of life score, and Children's Sleep Habits Questionnaire score. Results After 3 years of treatment, both groups showed significant improvements in all indicators from baseline (all P<0.05). The monosensitization group demonstrated greater improvements than the polysensitization group in peripheral blood eosinophil percentage, fractional exhaled nitric oxide, maximum mid-expiratory flow as a percentage of predicted value, Asthma Control Test scores, and quality of life scores (all P<0.05). The incidence of adverse reactions did not differ significantly between the two groups (P>0.05). Conclusions SCIT is effective in children with dust mite-allergic asthma, and monosensitized children show greater improvements in small airway function, asthma control, and quality of life.