〔Abstract〕 Objective To observe the clinical effect of interferon α1b combined with Xiaoer Chiqiao Qingre granules in the treatment of acute upper respiratory tract infection with leukopenia in children. Methods 80 children with acute upper respiratory tract infection with leukopenia admitted to Xinxiang Maternal and Child Health Hospital from January 2021 to December 2021 were selected and randomly divided into an observation group and a control group, with 40 cases in each group. The control group was treated with Xiaoer Chiqiao Qingre granules by oral administration, and the observation group was treated with interferon α1b aerosol inhalation on the basis of the control group. The children in the two groups were given general symptomatic treatment. The time of fever reduction, the time of leukocyte recovery to normal, the absolute normal rate of neutrophil and the incidence of complications were observed and compared between the two groups. Results The time of fever reduction and total white blood cell recovery in the observation group were shorter than those in the control group, and the differences were statistically significant (P < 0.05). After 5 days of treatment, the normal rate of neutrophil absolute value in the observation group was higher than that in the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in the incidence of complications between the two groups (P > 0.05). Conclusion Interferon α1b combined with Xiaoer Chiqiao Qingre granules in the treatment of acute upper respiratory tract infection in children with leukopenia can reduce clinical symptoms, shorten the course of the disease, and have good safety.