Objective To investigate the correlation of heat shock protein 27 (HSP27) and brain natriuretic peptide precursor (NT-proBNP) levels with chronic pulmonary heart disease (CPHD).Methods One hundred and twenty patients with CPHD disease (observation group) and 100 age- and sex-matched normal people were selected as the control group. The difference of serum HSP27 and NT-proBNP levels between the two groups observed, and the relationships of the levels of HSP27 and NT-proBNP with the cardiac function classification and prognosis of CPHD patients were analyzed.Results The levels of serum HSP27 and NT-proBNP in the observation group were higher than those in the control group (P < 0.05). The levels of serum HSP27 and NT-proBNP increased with the increase of NYHA cardiac function grade (P < 0.05). Follow-up was performed on all patients with CPHD in this group, and 12 died. The serum levels of HSP27 and NT-proBNP in the death group were higher than those in the survival group (P < 0.05). Multivariate logistic regression analysis showed that NYHA grade III and IV [R = 1.521 (95% CI: 1.302, 6.352)], HSP27 [R = 2.353 (95% CI: 1.564, 10.549)], and NT-proBNP [R = 2.754 (95% CI: 1.513, 12.356)] were the influencing factors of death in patients with CPHD. The AUC was 0.723 (95% CI：0.538，0.908), 0.859 (95% CI：0.807，0.911), and 0.876 (95% CI：0.742，1.000), and the sensitivity and specificity were 70.37%, 71.55%, 77.78%, 89.23%, 89.23%, 91.01%, respectively.Conclusion The levels of HSP27 and NT-proBNP were significantly increased in CPHD patients, and were closely related to the cardiac function and prognosis.