To observe the immediate craniocerebral response, changes of spontaneous nerve activity and functional connection after repeated transcranial magnetic stimulation (rTMS) in esophageal cancer patients with depression (ECPD) by functional magnetic resonance imaging (fMRI), and to explore the therapeutic effect, neuroactivity response and mechanism. Eleven patients with ECPD were enrolled to treated with single rTMS. The patients were examined by fMRI before and after the treatment. The changes of low frequency amplitude (ALFF) and the functional connection network between different brain regions of ALFF in patients were compared before and after rTMS treatment. Compared with those before rTMS treatment, the Hamilton Depression Rating Scale (HAMD) score decreased significantly after rTMS treatment (t = -7.63, P = .0001). The ALFF of bilateral putamen, left thalamus, left posterior cingulate gyrus and right middle temporal gyrus decreased significantly (P = .02). In addition, the functional connection between the cortex-limbic system-striatum-thalamus nerve loop increased in patients after rTMS treatment. rTMS may achieve the effect of rehabilitation treatment by improving the spontaneous neural activity and regulating the neural connection network of cortical-limbic systems-triatum-thalamus loop in ECPD.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.