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Background: Managing distress has become crucial in optimized cancer care. Psychoeducation using tablet PCs has potential as a novel intervention to reduce distress in cancer patients. We examined the benefit of a single-session psychoeducation using a tablet PC during chemotherapy., Methods: Thirty-six cancer patients with significant levels of distress, as determined by the Hospital Anxiety and Depression Scale (HADS), enrolled from the chemotherapy unit in Seoul National University Cancer Hospital. Participants were quasi-randomized into either the intervention (n = 19) or control (n = 17) group. Twenty-minute-long psychoeducation on distress management was provided via tablet PCs during chemotherapy infusion. HADS, Short-form 8 Health Survey, MD Anderson Symptom Inventory, Insomnia Severity Index, and Impact of Event Scale-Revised (IES-R) were administered at baseline and 3 weeks later. The use of psychosocial services was reviewed 6 months later., Results: Compared with controls, the intervention group showed a superior 3-week clinical trajectory regarding the score changes of the HADS depression subscale (U = 69.0; p = 0.006), mental component summary score of the Short-form 8 Health Survey (U = 75.5; p = 0.011), Impact of Event Scale-Revised avoidance subscale (U = 89.0; p = 0.036), and Insomnia Severity Index total score (U = 82.5; p = 0.021). There was no significant between-group difference regarding the use of psychosocial services after 6 months., Conclusions: A tablet PC-based psychoeducation during chemotherapy infusion could be an effective intervention on managing depression, sleep disturbance, and quality of life in cancer patients suffering from distress., (Copyright © 2014 John Wiley & Sons, Ltd.)