ABSTRACT Background Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for early detection and prompt initiation of medial therapy for CTRCD. There has been no study investigating whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with LVEF ≤ 50% were excluded. CTRCD was defined as ≥ 10% decline in LVEF and LVEF < 50% after chemotherapy. The angle between the anterior-wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. Results CTRCD was observed in 36 patients (22%). The average LVEF and GLS were lower (61.6 vs. 65.0%, 18.7 vs. 20.3), LV mass index was higher (101.1 vs. 92.8 g/m2), and ASA was smaller (112.1 vs. 119.4 degree) in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (HR per 1% decrease 1.20, 95% CI 1.07-1.35, P = 0.002), ASA (HR per 1 degree increase 0.97, 95% CI 0.95-0.99, P = 0.003) and the history of ischemic heart disease (HR 5.13, 95% CI 1.94-13.56, P = 0.001) were identified as the independent determinants of CTRCD. C-statistics analysis and integrated discrimination improvement proved the significant incremental value of ASA for developing CTRCD. Conclusion Smaller ASA was the independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.