Abstract: Objective To investigate the clinical efficacy and impact on psycho-behavioral aspects of sublingual immunotherapy with dermatophagoides farinae drops in children with multiple allergies and young-age allergic rhinitis (AR). Methods A total of 139 children with AR sensitized to mites who were treated at the Second Affiliated Hospital of Nanjing Medical University were retrospectively selected. Based on the types of allergens, they were divided into single-allergen group and multiple-allergen group, and into young-age group (≤4 years old) and older-age group (>4 years old) according to age. Visual Analogue Scale (VAS), Total Nasal Symptom Score (TNSS), Child Behavior Checklist (CBCL) score, and serum total immunoglobulin E (IgE) levels were compared before treatment and at 6 and 12 months after treatment. Results A total of 123 children completed one-year of sublingual immunotherapy and clinical observation. Compared with pre-treatment, the VAS scores, TNSS, and serum total IgE concentrations of children decreased at 6 and 12 months after desensitization treatment. Moreover, the VAS scores, TNSS, and serum total IgE concentrations at 12 months of treatment were lower than those at 6 months (P < 0.05). Compared with pre-treatment, after 12 months of desensitization treatment, the scores of social withdrawal, anxiety/depression, somatic complaints, and hyperactivity items in children decreased (P < 0.05). After 6 and 12 months of desensitization treatment, the VAS scores and TNSS in the multiple-allergen group were lower than those in the single-allergen group (P < 0.05). Compared with pre-treatment, the serum total IgE concentrations in both the single-allergen group and the multiple-allergen group decreased at 6 and 12 months after treatment, with statistically significant differences (P < 0.05). Before treatment, the serum total IgE concentration in the older-age group was higher than that in the young-age group (P < 0.05). Conclusion Sublingual immunotherapy can achieve significant efficacy in children with multiple allergies and young-age (≤4 years old) AR, and shows better efficacy in children with multiple allergies. Meanwhile, this treatment is also beneficial for reducing the occurrence of psycho-behavioral problems in children, especially for improving hyperactive behavior.