Importance <p>Perioperative depression is a psychological disorder prevalent in patients undergoing breast cancer surgery and is primarily characterized by feelings of depression or a lack of interest. There is a paucity of effective interventions for these conditions. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various depression-related disorders.</p> Objective <p>To investigate the efficacy of tDCS in alleviating perioperative depression in patients undergoing breast cancer surgery.</p> Design, setting, and participants <p>This randomized clinical trial was conducted between December 17, 2024, and March 28, 2025, in the Xuzhou Central Hospital. Patients aged 18 years or older undergoing elective breast cancer surgery were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in April 2025.</p> Interventions <p>Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex. Interventions were delivered daily, each morning, starting one day prior to surgery and continuing until the fifth postoperative day. Assessments of perioperative depression levels and sleep quality were conducted at baseline, the 5th day and 1st month after surgery. Additionally, the incidence of adverse reactions and postoperative NRS scores were evaluated.</p> Main outcomes and measures <p>The main outcome was HAMD-17(Hamilton Depression Rating Scale 17 items) scores on days 5 and 1 month after surgery. The secondary outcomes included the following: 1. BDI-13(Beck Depression Inventory 13 items) scores on days 5 and 1 month after surgery. 2. PSQI(Pittsburgh sleep quality index) on days 5 and 1 month after surgery. 3.NRS (Number Rating Scale) scores at rest and active states before surgery and 1–5 days after surgery. 4. Postoperative adverse reactions (end of the operation to the 5th day after the operation).</p> Results <p>A total of 64 patients were recruited and randomly assigned to the active tDCS group (32 patients) or the sham tDCS group (32 patients). Following the intervention, the active tDCS group showed a HAMD score of 4.67(1.75), which was significantly lower than that of the sham tDCS group’s 6.37(2.99) (<i>P</i> = 0.01). The active tDCS group showed significantly lower NRS scores than the sham tDCS group (<i>P</i> &lt; 0.001). The active tDCS group had a PSQI score of 3.57(1.59), which was significantly lower than that of the sham group (4.87(2.37); <i>P</i> = 0.016). Additionally, a significant difference (<i>P</i> = 0.018) was observed in the incidence of postoperative nausea and vomiting between the two groups.</p> Conclusions and relevance <p>tDCS can accelerate depressive symptoms relief during acute recovery and offer short-term benefits for early postoperative patients. The lack of group difference at 1 month reflects continued improvement in the sham group, not waning of the active effect. tDCS is a nonpharmacological adjunct to accelerate early recovery after breast cancer surgery.</p> Trial registration <p>Chinese Clinical Trial Register Identifier: ChiCTR 2500104410</p>