Objective To evaluate the effect of compound glycyrrhizin on the prevention and cure of cytarabine syndromes. Methods A total of 130 patients with hematological malignancies treated by moderate or high dose of cytarabine in the 303th Hospital of PLA from July 2010 to July 2016 were included. Patients were randomly divided into the control group and the experiment group by using random number table method, and each group had 65 patients. In the control group, patients were treated with cytarabine alone. In the experiment group, patients were treated with cytarabine plus compound glycyrrhizin. Skin rash and fever in patients of the two groups were also recorded. Results of blood routine tests, liver and kidney function tests were monitored during the treatment. Results Sixty-one patients in the experiment group and 63 patients in the control group were enrolled finally. In experiment group and control group, the differences in the incidence of cytarabine syndromes [8.2 % (5/61) vs. 41.3 % (26/63), χ2＝ 18.1, P < 0.001], skin rash [1.6 % (1/61) vs. 12.7 % (8/63), χ2＝16.3, P <0.001], and fever [6.6 % (4/61) vs. 36.5 % (23/63), χ2＝5.63, P <0.017] were statistically significant. There was no significant difference of the incidence of liver injury and minimum blood cell count between the two groups (P＞ 0.05). Conclusion Compound glycyrrhizin can effectively reduce the incidence of cytarabine syndromes, but the larger size and multiple center studies are needed to further verify the effect.