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Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer. wellbeing, wellbeing being, being unresectable 22 care n=112 n112 n 112 n=110 n110 110 6month intervention HADSA HADS (HADS-A HADSD, HADSD D , (HADS-D) TherapySpiritual Therapy Spiritual WellBeing Well Being FACITSp, FACITSp FACIT Sp (FACIT-Sp) QuestionnaireCore Questionnaire Core 3 QLQC30 QLQC QLQ C30 C (QLQ-C30 M0, M0 M 0, 0 (M)0 outcome P=0.005. P0005 P P=0.005 . 005 (P=0.005) outcomes all P<0.050. P0050 P<0.050 050 P<0.050) Additionally QLQ-C3 P=0.046 P0046 046 (P=0.046 P=0.005, P=0.038, P0038 P=0.038 038 (P=0.038) P=0.019 P0019 019 (P=0.019 baseline summary 2 n=11 n11 11 (HADS-D (FACIT-Sp QLQC3 C3 (QLQ-C3 (M) P000 P=0.00 00 (P=0.005 P005 P<0.05 05 QLQ-C P=0.04 P004 04 (P=0.04 P003 P=0.03 03 (P=0.038 P=0.01 P001 01 (P=0.01 n=1 n1 1 (QLQ-C (M P00 P=0.0 (P=0.00 P<0.0 (P=0.0 (P=0.03 n= P0 P=0. P<0. (P=0. P=0 P<0 (P=0 P= P< (P= (P