Background Early screening and diagnosis of radiation-induced heart disease are difficult in patients with chest radiation exposure. sST2 involved in myocardial stress or injury. We aimed to evaluate short-term sST2, B-type natriuretic peptide (BNP) and the left ventricle ejection fraction (LVEF) changes and the relationship between sST2 and heart dose in patients who receive chest radiation. Methods We prospectively collected thoracic malignancy cancer patients from October 2016 to August 2018 who received chest radiotherapy. sST2 and BNP was measured before (recorded as preST2, preBNP), in the middle (recorded as midST2, midBNP) and after radiotherapy (recorded as postST2, postBNP). LVEF was detected using echocardiography before and after radiotherapy. BNP and sST2 among pre, mid, post groups were compared using nonparametric test. LVEF was compared using pair t-test. Standardized sST2 was calculated as postsST2/presST2. The correlation of standardized sST2 and heart dosimetry parameters were measured by Spearman’s correlation test. Results Sixty patients were enrolled, including 37(61.67%) lung cancer, 18(30.00%) esophageal cancer and 5 (8.33%) thymoma patients. The median preST2, midST2, postST2 was 3.86 (IQR1.56-8.37), 6.33 (IQR 2.01-9.32) and 8.00 (IQR 4.2- 10.9) respectively. sST2 elevated with the progression of thoracic irradiation (p<0.001). The median preBNP, midBNP and postBNP was 22.56 (IQR 7.25-63.5), 32.25 (IQR 18.85-52.97) and 32.41 (IQR 17.23-55.97), respectively. The mean preLVEF and postLVEF was 64.36 and 62.76, respectively. There was no significant change in BNP and LVEF after radiotherapy. Standardized sST2 was correlation with V5Gy, V10Gy, V20Gy, V30Gy, mean heart dose and left anterior descending artery (LAD) (V5Gy rs = 0.541, p = 0.00; V10Gy rs = 0.504, p = 0.00; V20Gy rs = 0.437, p = 0.001; V30Gy, rs = 0.305, p = 0.026; mean heart dose rs = 0.395, p = 0.003 and mean heart dose of LAD rs = 0.414, p = 0.002). Conclusion BNP and LVEF were not changed after thoracic radiation. Serum sST2 levels were elevated during radiotherapy and associated with heart dose parameters in thoracic malignant tumor patients. sST2 would be regarded as a potential early diagnostic marker for RIHD.