PURPOSE: Insomnia is highly prevalent among cancer survivors and can have serious implications if inadequately treated. Cognitive-behavioral therapy for Insomnia (CBT-I) is recommended as the first-line treatment for insomnia but is rarely available to cancer survivors. We tested the effectiveness of a web-based CBT-I program, OncoSleep, in cancer survivors. METHODS: Cancer survivors with insomnia (n = 154) were randomly assigned (1:1) to digital CBT-I (6 weekly self-guided modules plus online clinician support) or a waitlist control group. Patient-reported outcome measures of insomnia severity (primary outcome), daytime functioning, and sleep diaries were administered online at baseline and post-treatment (8 weeks). Intention-to-treat analyses were performed using mixed-effects models. Statistical tests were two-sided. RESULTS: The treatment group reported an average 11.0-point reduction in the Insomnia Severity index (ISI), compared to a 1.4-point reduction in the control group (p<
.001). Statistically significant group-by-time interactions were observed: web-based CBT-I produced significant, large effects for improvements in insomnia severity (d = -2.56), cognitive functioning (d = 0.95), physical (d = 1.24) and psychological quality of life (d = 0.80), and fatigue (d = -1.35). Small-to-large effect sizes were found for reductions in anxiety (d = -0.77), depression (d = -0.71), and pain (d = -0.40). Change in insomnia severity mediated the effect of digital CBT-I on daytime outcomes. CONCLUSIONS: Web-based CBT-I with clinician support appears to be an effective treatment for insomnia in cancer survivors, offering meaningful benefits for comorbid symptoms and quality of life. Further studies with active comparisons and longer follow-up periods are needed to confirm these findings. Digital CBT-I could be integrated into cancer rehabilitation programs to reduce the burden of insomnia. [ClinicalTrials.gov: NCT04898855].