Hypertrophic cardiomyopathy (HCM) is the most common chromosomal abnormal heart disease. The pathophysiological mechanism of HCM is complex. Several studies have suggested that the level of Soluble ST2 (sST2) may be a biomarker of chronic systolic heart failure, however, the role of sST2 in HCM remains unclear. So we performed this study to analyze the role of Soluble ST2 (sST2), Galectin-3 (Gal-3) and its correlations with clinical prognosis of patients with hypertrophic cardiomyopathy (HCM) undergoing ventricular septal myectomy. HCM patients who underwent modified Morrow surgery in our hospital during June 2016-June 2018 were included. We divided the patients into different groups stratified by sST2 and Gal-3 level. Besides, we included volunteers without heart disease for medical examination as normal controls. Biochemical analyses were conducted to identify the biomarkers difference. The predictive value of sST2 and Gal-3 on all-cause mortality was evaluated with Cox regression analysis. A total of 125 HCM patients were included in this present study. The sST2 and Gal-3 levels in HCM patients were significantly higher than that in control group (all P<0.001); there were significant differences in the incidence of all-cause mortality for HCM patients stratified by the sST2 and Gal-3 level; Cox univariate regression survival analysis showed that the hypertension (HR =1.19, 95% CI: 1.01-1.38), maximum wall thickness (HR =1.48, 95% CI: 1.04-1.98), Log sST2 (HR =1.02, 95% CI: 1.01-1.05), Log Gal-3 (HR =1.17, 95% CI: 1.09-1.32) were the predictors for all-cause mortality in patients with HCM, and Cox multivariate risk regression showed that maximum wall thickness was the independent predictors of all-cause mortality in patients with HCM (HR =1.63, 95% CI: 1.35-1.97). Even through sST2 and Gal-3 were not associated with clinical prognosis of patients with HCM undergoing ventricular septal myectomy, it may be involved in the progress of HCM, more studies are warranted to identify the potential mechanism and reverence value. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.