To explore the efficacy and safety of sublingual house dust mite (HDM) drops in children with mono- or polysensitized allergic rhinitis. We conducted a retrospective cohort study of 65 children with monosensitized AR and 118 children with polysensitized AR who were scheduled for sublingual administration of HDM drops from January 2015 to June 2016. Interleukin (IL)-2, IL-4, and IL-17α, transforming growth factor-β1 (TGF-β1), specific immunoglobulin E (IgE), and specific IgG4 were detected by ELISA. The efficacies were assessed using symptoms score and medication score. All the outcomes were measured 1 month before the study and 1 month after the end of the 2-year treatment. The total nasal symptoms score (TNSS) decreased significantly from 11.27 (9.81 ± 12.73) at baseline to 3.48(1.98 ± 4.98) at the end of sublingual treatment for the monosensitized AP group (t = 30.00, P < 0.01), and from 11.54(10.04 ± 13.04) to 3.56 (2.00 ± 5.16) for the polysensitized AR group (t = 40.05, P < 0.01), respectively. IL-2 and TGF-β1 increased significantly after treatment in contrast with before treatment in both the monosensitized group and the polysensitized group (both P < 0.01). In contrast, IL-4 and IL-17α decreased significantly after treatment compared with the baseline in both groups (both P < 0.01). Sublingual HDM drops were generally safe and well tolerant in both groups. This study confirmed the efficacy and safety of sublingual AIT in both monosensitized and polysensitized AR patients (Chinese children).