To assess the clinical effect of astragalus polysaccharide in preventing cardiotoxicity induced by chemotherapy of epirubicin. Two hundred forty-eight patients with breast cancer or malignant lymphoma were randomly divided into the experimental group (EG) (n = 124) and the control group (CG) (n = 124). The EG received chemotherapy regimen containing anthracycline epirubicin and astragalus injection, while CG received only chemotherapy regimen containing anthracycline epirubicin. We detected myocardial function (cardiac troponin I [cTnI], creatine kinase isoenzyme [CK-MB], left ventricular ejection fraction [LVEF], and the ratio of mitral annular diastolic peak velocity to atrial systolic velocity [E/A]) and incidences of cardiotoxicity to assess cardiac function, they were compared at before the first treatment course (T
1
), end of the second course (T
2
) and 6-month follow-up. We also detected proinflammatory cytokines (IL-6 and TNF-α), reactive oxygen species and antioxidant enzymes, glutathione peroxidase (GPx), and superoxide dismutase (SOD) aimed to discover potential mechanism. There were no statistical significances in differences of LVEF and E/A between 2 groups (
P
> .05) at T
1
and T
2
, while levels of LVEF and E/A of EG were significant higher than those of the CG at 6 month follow-up, with statistically significant differences (
P
< .05). At T
1
, there were no statistical significances in differences of cTnI and CK-MB between 2 groups (
P
> .05); at T
2
and 6 months follow-up, the cTnI, and CK-MB levels of EG was significantly lower than those of the CG, with statistically significant differences (
P
< .05). The incidence of cardiotoxicity of EG was 15% (17/113), which was significant lower than that of the CG (60%, 66/110), with statistically significant difference (
P
< .05). Moreover, the level of TNF-α, GPx, and SOD did not show significant difference (
P
> .05). The data in this pilot study suggested that astragalus polysaccharide may be an effective therapy for preventing cardiotoxicity induced by chemotherapy of epirubicin. Furthermore, larger, placebocontrolled, perspective studies are needed to assess the efficacy of astragalus injection treatment for preventing cardiotoxicity induced by chemotherapy of epirubicin.