Generalized anxiety disorder (GAD) is a chronic mood disease associated with abnormal brain network connections, including decreased activity in the left dorsolateral prefrontal cortex (DLPFC). Cortical excitability can be increased with 820-nm transcranial near-infrared stimulation (tNIRS), while transcranial magnetic stimulation with electroencephalography (TMS-EEG) can help evaluate time-varying brain network connectivity. A randomized, double-blind, sham-controlled trial was conducted to assess the efficacy of tNIRS on the left DLPFC and the impact on time-varying brain network connections in GAD patients.A total of 36 GAD patients were randomized to receive active or sham tNIRS for 2 weeks. Clinical psychological scales were assessed before, after, and at the 2-, 4-, and 8-week follow-ups. TMS-EEG was performed for 20 min before and immediately after tNIRS treatment. The healthy controls did not receive tNIRS and only had TMS-EEG data collected once in the resting state.The Hamilton Anxiety Scale (HAMA) scores of the active stimulation group decreased post-treatment compared with the sham group (P = 0.021). The HAMA scores of the active stimulation group at the 2-, 4-, and 8-week follow-up assessments were lower than those before treatment (P < 0.05). The time-varying EEG network pattern showed an information outflow from the left DLPFC and the left posterior temporal region after active treatment.Herein, 820-nm tNIRS targeting the left DLPFC had significant positive effects on therapy for GAD that lasted at least 2 months. tNIRS may reverse the abnormality of time-varying brain network connections in GAD.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.