Background Most patients with cancer experience psychological or physical distress, which can adversely affect their quality of life (QOL). Smartphone app interventions are increasingly being used to improve QOL and psychological outcomes in patients with cancer. However, there is insufficient evidence regarding the effect of this type of intervention, with conflicting results in the literature. Objective In this systematic review and meta-analysis, we investigated the effectiveness of mobile phone app interventions on QOL and psychological outcomes in adult patients with cancer, with a special focus on intervention duration, type of cancer, intervention theory, treatment strategy, and intervention delivery format. Methods We conducted a literature search of PubMed, Web of Science, the Cochrane Library, Embase, Scopus, China National Knowledge Infrastructure, and WanFang to identify studies involving apps that focused on cancer survivors and QOL or psychological symptoms published from inception to October 30, 2022. We selected only randomized controlled trials that met the inclusion criteria and performed systematic review and meta-analysis. The standardized mean difference (SMD) with a 95% CI was pooled when needed. Sensitivity and subgroup analyses were also conducted. Results In total, 30 randomized controlled trials with a total of 5353 participants were included in this meta-analysis. Compared with routine care, app interventions might improve QOL (SMD=0.39, 95% CI 0.27-0.51; P<.001); enhance self-efficacy (SMD=0.15, 95% CI 0.02-0.29; P=.03); and alleviate anxiety (SMD=−0.64, 95% CI −0.73 to −0.56; P<.001), depression (SMD=−0.33, 95% CI −0.58 to −0.08; P=.009), and distress (SMD=−0.34, 95% CI −0.61 to −0.08; P=.01). Short-term (duration of ≤3 months), physician-patient interaction (2-way communication using a smartphone app), and cognitive behavioral therapy interventions might be the most effective for improving QOL and alleviating adverse psychological effects. Conclusions Our study showed that interventions using mobile health apps might improve QOL and self-efficacy as well as alleviate anxiety, depression, and distress in adult cancer survivors. However, these results should be interpreted with caution because of the heterogeneity of the interventions and the study design. More rigorous trials are warranted to confirm the suitable duration and validate the different intervention theories as well as address methodological flaws in previous studies. Trial Registration PROSPERO CRD42022370599; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=370599
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