Background: Despite its efficacy in treating comorbid insomnia and depression, cognitive behavioral therapy for insomnia (CBT-I) is limited in its accessibility and, in many regions, cultural compatibility. Smartphone-based treatments is a low-cost, convenient alternative modality. This study evaluated a self-help smartphone-based CBT-I in alleviating major depression and insomnia.Methods: A parallel-group randomized, waitlist-controlled trial was conducted with 322 adults with major depression and insomnia. Participants were randomized to receive either a 6-week CBT-I via a smartphone application, proACT-S, or waitlist condition. The primary outcomes included depression severity, insomnia severity, and sleep quality. The secondary outcomes included anxiety severity, subjective health, and acceptability of treatment. Assessments were administered at baseline, post-intervention follow up (Week 6), and Week 12 follow-up. The waitlist group received treatment after the first follow-up.Results: Intention to treat analysis was conducted with multilevel modeling. In all but one models, the interaction between treatment condition and the time point at Week 6 follow-up was significant. Compared with the waitlist group, the treatment group had lower levels of depression (CES-D: treatment difference = 0.83, 95% CI [0.58, 1.09]), insomnia (ISI: treatment difference = 0.89, 95% CI [0.64, 1.16]), and anxiety (HADS-A: treatment difference = 0.80, 95% CI [0.55, 1.06]). They also had better sleep quality (PSQI: treatment difference = 0.84, 95% CI [0.58, 1.10]). No differences across any measures were found at Week 12, after the waitlist control group received the treatment. Conclusion: proACT-S is an efficacious sleep-focused self-help treatment for major depression and insomnia.