Abstract: OBJECTIVE To analyze the drug-drug interaction during the use and treatment of nirmatrelvir/ritonavir tablets in children, and to provide reference for rational drug use in clinical practice. METHODS All hospitalized pediatric patients with using nirmatrelvir/ritonavir tablets from December 23, 2022 to February 8, 2023 in Children's Hospital, Zhejiang University School of Medicine were collected. The use of nirmatrelvir/ritonavir was analyzed, and the combination drugs were classified. The potential clinical drug-drug interactions of nirmatrelvir/ritonavir were analyzed through micromedex drug interaction database and the severity was graded. RESULTS A total of 48 patients using nirmatrelvir/ritonavir tablets were collected, with a median age of 6.71 years old(87 d-17.75 years old). The usage departments were mainly in the departments of hematology, ICU, infectious disease, and general internal medicine, and the main underlying disease being tumors. The median fever-reducing time after medication was 3 d. Many drugs were combined during medication period. A total of 15 potential drug-drug interaction drugs of nirmatrelvir/ritonavir tablets were collected, and potential drug interaction with antifungals should be considered. CONCLUSION The department with more usage of nirmatrelvir/ritonavir tablets in children is hematology, and the main underlying disease is tumors. When nirmatrelvir/ritonavir tablets are used in combination with potential drug-drug interaction drugs, attention should be paid to monitoring the efficacy and adverse reactions.