Heart failure (HF) is a clinical cardiovascular disease occurred frequently in clinic with high morbidity and mortality. In the present study effect and mechanism of sacubitril valsartan sodium tablets (SVST) in the treatment of heart failure was investigated. The study recruited 200 samples with HF from May 2020 to Dec 2021, and assigned them to a research group and a control group which was given routine angiotensin-converting enzyme inhibitors (ACEI) after admission. Research group was additionally given SVST. The two arms were compared with different items. Besides, NF-xB and iNOS mRNA contents were measured by PCR. The clinical efficacy and incidence of ARs differed insignificantly between the two arms. After 1 and 3 months of treatment, E/A and LVEF were higher while LVESD, LVEDd, NT-pro BNP, cTnI and CRP were lower in RG compared with CG. In addition, NF-xB and iNOS mRNA contents were lower in RG than in CG, and their levels showed a time-dependent decrease. Thus, SVST is safe in the treatment of HF and can facilitate the recovery of patients, the mechanism may be related with regulation of NF-xB and iNOS.