Patients receiving chemotherapy for breast cancer may be at risk of developing cardiac dysfunction and electrophysiological abnormalities. The aim of this study is to evaluate alterations in electrocardiographic (ECG) parameters in breast cancer patients receiving chemotherapy. This was a prospective single-center cohort study conducted in the Fourth Hospital of Hebei Medical University, China. Participants with breast cancer referred for chemotherapy from May 1, 2019, to October 1, 2019, were invited to participate in the study. Standard 12-lead ECG and echocardiography were performed at baseline or before chemotherapy (prechemotherapy) (T0), after 1 cycle (T1), after 3 cycles (T2), and at the end of chemotherapy (T3). A total of 64 patients with diagnosed breast cancer undergoing chemotherapy were included. Echocardiographic parameters showed no significant variation during the entire procedure (all P > 0.05). The incidence of abnormal ECG increased from 43.75% at baseline to 65.63% at the end of chemotherapy, of which only the prevalence of fragmented QRS (fQRS) was significantly increased after the drug regimen (26.56% to 53.13%). At the end of the treatment, heart rate, P-wave dispersion, corrected QT interval, T-peak to T-end, RR, SV1, RV5, Sokolow-Lyon index (SLI), and index of cardioelectrophysiological balance deteriorated markedly (all P < 0.05). The area under the curve for SLI and QT dispersion (QTd) derived by ECG was 0.710 and 0.606, respectively. The cutoff value with 2.12 of SLI by ECG had a sensitivity of 67.2% and specificity of 71.9% for differentiating patients after therapy from baselines. The cutoff value with 0.55 of QTd had a sensitivity of 60.9% and specificity of 60.9%. The current study demonstrated that ECGs can be used to detect electrophysiological abnormalities in breast cancer patients receiving chemotherapy. ECG changes can reflect subclinical cardiac dysfunction before the echocardiographic abnormalities. Copyright © 2020 Xufei Liang et al.