Background: In addition to the physical burden, the quality of life and survival in patients with cancer may also be reduced because of psychological distress, such as spiritual crisis, anxiety, and depression. Many studies have verified that spirituality could reduce anxiety and depression and improve quality of life and adjustment to cancer. However, there is uncertainty regarding the effectiveness of spiritual interventions in patients with cancer. The purpose of this meta-analysis is to use randomized controlled trials (RCTs) to evaluate the effects of spiritual interventions on spiritual and psychological outcomes and quality of life in patients with cancer. Methods: All RCTs using spiritual interventions relevant to the outcomes of patients with cancer were retrieved from the following databases: Embase, PubMed, PsycINFO, Ovid, Springer Online Library, Wiley Online Library, Oxford Journals, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The reference lists of identified RCTs were also screened. The Cochrane risk of bias tool was used to evaluate the quality of the studies, RevMan (5.3) was used to analyze the data, and GRADE (3.6.1) was used to evaluate the evidence quality of the combined results. Results: Ten RCTs involving 1239 patients were included. Spiritual interventions were compared with a control group receiving usual care or other psychosocial interventions. The weighted average effect size across studies was 0.46 (P = .003, I = 78%) for spiritual well-being, 0.19 (P = .005, I = 46%) for quality of life, -0.33 (P = .01, I = 50%) for depression, -0.58 (P = .03, I = 77%) for anxiety, and -0.38 (P = .008, I = 0%) for hopelessness. In subgroup analysis according to the type of cancer, only the weighted average effect size of spiritual well-being in patients with breast cancer had statistical significance (standardized mean difference 0.78, P = .01, I = 70%). Conclusion: Spiritual interventions may improve spiritual well-being and quality of life, and reduce depression, anxiety, and hopelessness for patients with cancer. However, due to the mixed study design and substantial heterogeneity, some evidence remains weak. More rigorously designed research is needed.