OBJECTIVE：To observe the clinical efficacy and safety of compound glycyrrhizin combined with acyclovir in the treatment of children with infectious mononucleosis. METHODS： 90 children with  infectious mononucleosis were randomly divided into control group and research group. Control group was given Acyclovir injection 10 mg/（kg·d） adding into 150 ml 5％ Glucose solution by intravenous infusion， twice a day. Research group was additionally given Compound glycyrrhizin injection 2-4 ml/kg， adding into 150 ml 5％ Glucose solution by intravenous infusion， twice a day. The treatment course for both group was 2 weeks. Clinical efficacy， hospitalization time， improvement time of clinical symptoms，T lymphocyte subsets （CD3+，CD4+，CD8+ and CD4+/CD8+） before and after treatment and incidence of adverse reactions in 2 groups were observed. RESULTS： The total effective rate in research group was significantly higher than control group， hospitalization time and improvement time of clinical symptoms were significantly better than control group， the differences were statistically significant（P＜0.05）. After treatment， CD3+ and CD8+ were significantly lower than before， and research group was lower than control group， CD4+ and CD4+/CD8+ were significantly higher than before， and research group was higher than before， the differences were statistically significant（P＜0.05）. There was no significant difference in the incidence of adverse reactions between 2 groups（P＞0.05）. CONCLUSIONS： Compound glycyrrhizin combined with acyclovir has better efficacy than only acyclovir in the treatment of children with infectious mononucleosis， with similar safety.