Background <p>Pranayama breathing exercises may help reduce the burden of chemotherapy-induced symptoms in women with breast cancer. The aim of this study was to determine the effect of pranayama breathing exercise on symptom burden in women with breast cancer undergoing chemotherapy.</p> Methods <p>In this clinical trial, 76 participants were randomly assigned to two groups: pranayama breathing exercise plus routine care (intervention group) (<i>n</i> = 38) or routine care (control group) (<i>n</i> = 38). Patients were asked to perform pranayama breathing twice a day for 10 min for 21 days (one week before chemotherapy to 14 days after the start of chemotherapy). Symptom burden was measured through the MD Anderson Symptom Inventory (MDASI) before the intervention, on the first day of chemotherapy, on day 7 and on day 14 after chemotherapy.</p> Results <p>A significant decrease in the total score of symptom burden and subscales of symptom severity and symptom interference with daily activities was shown in the intervention group compared with the control group at all three measurement points (η² = 0.431, η² = 0.311, η² = 0.489, <i>P</i> &lt; 0.001, respectively). Among the symptoms, there was no significant difference in the mean score of dry mouth (<i>P</i> &lt; 0.744, η² = 0.002) and numbness and tingling (<i>P</i> &lt; 0.302, η² = 0.02) between the intervention and control groups.</p> Conclusions <p>Pranayama breathing exercise was effective in reducing the symptom burden in women with breast cancer undergoing chemotherapy. It is recommended that the pranayama breathing be considered as a component of comprehensive cancer care. Nurses should teach patients pranayama breathing as an independent nursing intervention to reduce the burden of chemotherapy-induced symptoms.</p> Trial registration <p>This trial has been registered on the Iranian Registry of Clinical Trials (<a href="http://www.irct.ir">http://www.irct.ir</a>) with the identifier (IRCT20231212060343N1). Registered date: 23/01/2023.</p>