〔Abstract〕 Objective To investigate the efficacy of lyophilized recombinant human brain natriuretic peptide in the treatment of chronic heart failure and analyze its mechanism. Methods A total of 108 patients with chronic heart failure who were admitted to the First Affiliated Hospital of Xinxiang Medical College from February 2020 to February 2021 were selected for this study. The patients were divided into two groups with 54 cases in each group by double chromosphere method. The control group received routine treatment, and the observation group was treated with freeze-dried recombinant human brain natriuretic peptide on the basis of control group. Clinical efficacy, cardiac function indexes, soluble growth stimulation expresses the gene 2 protein (sST2), galactose agglutinin 3 (Gal-3) and incidence of adverse reactions were compared between the two groups. Results After treatment, the total effective rate of the observation group was 92.60%, higher than 77.78% of the control group, the difference was statistically significant (P < 0.05); Cardiac function indexes in the two groups were improved compared with before treatment, and atrial inner diameter, left ventricular end-systolic diameter and left ventricular end-diastolic diameter in the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). sST2 and Gal-3 in the two groups were lower than those before treatment, and sST2 and Gal-3 in the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups during treatment (P > 0.05). Conclusion Chronic heart failure patients treated with freeze-dried recombinant human brain natriuretic peptide on the basis of conventional treatment have better curative effect than conventional treatment alone. Its mechanism of action may be related to that freeze-dried recombinant human brain natriuretic peptide can improve cardiac function indexes and reduce sST2, Gal-3 level.