Aim To investigate the effects of Qiliqiangxin capsule on oxidative stress and expressions of miRNA-21 (miR-21) and miRNA-145 (miR-145) in peripheral blood of patients with coronary heart disease and heart failure.Methods The 86 patients with coronary heart disease and heart failure admitted to our hospital from January 2017 to December 2018 were selected as the study subjects. They were randomly divided into control group (43 cases) and observation group (43 cases) by random number table method. The patients in the control group were treated with routine therapy, while the patients in the observation group were treated with Qiliqiangxin capsule on the basis of the control group. Both groups were treated for 4 weeks. The therapeutic effect, cardiac function, BNP, oxidative stress indexes and the expressions of miR-21 and miR-145 in peripheral blood before and after treatment were compared between the two groups.Results The total effective rate of the observation group was higher than that of the control group (93.02% vs 72.09%, P＜0.05). After treatment, the left ventricular end-diastolic diameter and left ventricular end-systolic diameter in the observation group were lower than those in the control group, while the left ventricular ejection fraction was higher than that in the control group (P＜0.05). The level of BNP in the two groups after treatment was lower than that before treatment (P＜0.05); After treatment, the level of BNP in the observation group was significantly lower than that in the control group (P＜0.05). The level of malondialdehyde (MDA) in the two groups after treatment was lower than that before treatment, while the level of superoxide dismutase (SOD) was higher than that before treatment (P＜0.05); After treatment, the MDA level of the observation group was lower than that of the control group, while the SOD level was higher than that of the control group (P＜0.05). The expressions of miR-21 and miR-145 in peripheral blood of the two groups after treatment was lower than that before treatment (P＜0.05); After treatment, the expressions of miR-21 and miR-145 in the peripheral blood of the observation group was lower than that of the control group (P＜0.05). After 3-10 months follow-up, the rates of readmission and mortality in the observation group were lower, and its readmission rate was significantly lower than that in the control group (P＜0.05). Conclusion Qiliqiangxin capsule has a good therapeutic effect on patients with coronary heart disease and heart failure, and it can reduce the level of plasma BNP, oxidative stress injury and the expressions of miR-21 and miR-145 in peripheral blood.